MARIA ASUNCION PERAL CERDA - Academia.edu (original) (raw)
Papers by MARIA ASUNCION PERAL CERDA
Drug News Perspectives, Apr 1, 2008
Dry eye is a multifactorial disease of the tears and the ocular surface that manifests with a wid... more Dry eye is a multifactorial disease of the tears and the ocular surface that manifests with a wide variety of signs and symptoms. It is prevalent in about 33% of the population worldwide. Due to the importance of the pathology, new tests, drugs and technologies have been developed to assist the diagnosis, management and follow-up of the disease. Current available therapies try to alleviate symptoms and to reduce signs in order to restore the ocular surface. Depending on the etiology of the pathology it is possible to use lubricants, secretagogues, biological tear substitutes or antiinflammatory drugs, either independently or combined. Nowadays, the therapies under clinical trial are devoted to stimulating tear components (e.g., diquafosol, a P2Y receptor agonist), or mucin secretion (e.g., rebamipide, an amino acid analogue of quinolinone). Others include gefarnate, a water-insoluble terpene fatty acid that contributes to restoring mucins on the ocular surface, or cevimeline, an oral cholinergic agonist that reduces the symptoms associated with dry eye. Other potential compounds described in patents are in a lower phase of drug development. These compounds come from different families of therapies, and among others, can be found in the form of steroidal and nonsteroidal antiinflammatory agents, vitamins A and D, neurotransmitters and neuropeptides.Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.
European Journal of Pharmacology, Jan 28, 2008
Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-dipho... more Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-diphosphate, UDP, for modulating IOP in New Zealand white rabbits. Uridine 5′ diphosphate, UDP, reduced IOP by 82.9 ± 2.6% compared to control. Dose-response analysis demonstrated a concentration dependent pattern which presented a pD 2 value of 7.57 ± 1.45, equivalent to an EC 50 of 26.91 nM. Of all the tested P2 receptor antagonists, suramin, pyridoxalphosphate-6-azophenyl-2, 4-disulfonic acid (PPADS) and Reactive Blue 2 (RB-2), only the last two were able to reverse the action triggered by UDP. Altogether, UDP acting probably on P2Y 6 receptors present on the ciliary processes, can reduce intraocular pressure, indicating that this substance may be used for the treatment of ocular hypertension and glaucoma.
European Journal of Pharmacology, Jan 28, 2008
Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-dipho... more Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-diphosphate, UDP, for modulating IOP in New Zealand white rabbits. Uridine 5′ diphosphate, UDP, reduced IOP by 82.9 ± 2.6% compared to control. Dose-response analysis demonstrated a concentration dependent pattern which presented a pD 2 value of 7.57 ± 1.45, equivalent to an EC 50 of 26.91 nM. Of all the tested P2 receptor antagonists, suramin, pyridoxalphosphate-6-azophenyl-2, 4-disulfonic acid (PPADS) and Reactive Blue 2 (RB-2), only the last two were able to reverse the action triggered by UDP. Altogether, UDP acting probably on P2Y 6 receptors present on the ciliary processes, can reduce intraocular pressure, indicating that this substance may be used for the treatment of ocular hypertension and glaucoma.
Progress in Retinal and Eye Research, Nov 30, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5'-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Progress in Retinal and Eye Research, Nov 30, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5'-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Archivos de la Sociedad Española de Oftalmología, 2007
Archivos de la Sociedad Española de Oftalmología, 2007
Acta Ophthalmologica, 2014
Purpose: To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to... more Purpose: To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to estimate the ocular surface changes associated with congenital aniridia compared to normal individuals. Methods: Fifteen patients diagnosed with congenital aniridia and a control group of forty volunteers were studied. Tears were collected to quantify the levels of diadenosine polyphosphates Ap 4 A and Ap 5 A by high-performance liquid chromatography (H.P.L.C). Break-up time (BUT), corneal staining, McMonnies questionnaire and the Schirmer I test were applied to both groups. Results: Dinucleotides in congenital aniridia patients were higher than in control subjects. For the congenital aniridia group, under 15 years old, the values were 0.77 AE 0.01 lM and 0.17 AE 0.02 lM for Ap 4 A and Ap 5 A, respectively. The group aged from 15 to 40 years old provided concentrations of 4.37 AE 0.97 lM and 0.46 AE 0.05 lM for Ap 4 A and Ap 5 A, the group over 40 gave concentrations of 11.17 AE 5.53 lM and 0.68 AE 0.17 lM for Ap 4 A and Ap 5 A. Dinucleotide concentrations increased with age, being statistically significant different among the three age groups (p < 0.05). Congenital aniridia patients showed a normal tear secretion and no dry eye McMonnies scores, except for the group over 40 years old. BUT values decreased and corneal staining increased with age and correlated with the levels of diadenosine polyphosphates (p < 0.05). Conclusions: The levels of dinucleotides in tears increase in aniridia patients compared with healthy subjects, and they seem to be related with the progression of corneal disorders in aniridia patients, both of which increase with ageing.
Acta Ophthalmologica, 2014
To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to estimate... more To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to estimate the ocular surface changes associated with congenital aniridia compared to normal individuals. Fifteen patients diagnosed with congenital aniridia and a control group of forty volunteers were studied. Tears were collected to quantify the levels of diadenosine polyphosphates Ap4 A and Ap5 A by high-performance liquid chromatography (H.P.L.C). Break-up time (BUT), corneal staining, McMonnies questionnaire and the Schirmer I test were applied to both groups. Dinucleotides in congenital aniridia patients were higher than in control subjects. For the congenital aniridia group, under 15 years old, the values were 0.77 ± 0.01 μm and 0.17 ± 0.02 μm for Ap4 A and Ap5 A, respectively. The group aged from 15 to 40 years old provided concentrations of 4.37 ± 0.97 μm and 0.46 ± 0.05 μm for Ap4 A and Ap5 A, the group over 40 gave concentrations of 11.17 ± 5.53 μm and 0.68 ± 0.17 μm for Ap4 A and Ap5 A. Dinucleotide concentrations increased with age, being statistically significant different among the three age groups (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Congenital aniridia patients showed a normal tear secretion and no dry eye McMonnies scores, except for the group over 40 years old. BUT values decreased and corneal staining increased with age and correlated with the levels of diadenosine polyphosphates (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The levels of dinucleotides in tears increase in aniridia patients compared with healthy subjects, and they seem to be related with the progression of corneal disorders in aniridia patients, both of which increase with ageing.
Purinergic Signalling, 2004
Nucleotides present an important role in ocular physiology, which has been demonstrated by recent... more Nucleotides present an important role in ocular physiology, which has been demonstrated by recent works that indicate their involvement in many ocular processes. P2Y are important among P2 receptors since they can control tear production, corneal wound healing, aqueous humour dynamics and retinal physiology. Commercial antibodies have allowed us to investigate the distribution of P2Y receptors in the cornea, anterior and posterior chamber of the eye and retina. The P2Y 1 receptor was present mainly in cornea, ciliary processes, and trabecular meshwork. The P2Y 2 receptors were present in cornea, ciliary processes and retinal pigmented epithelium. P2Y 4 was present in cornea, ciliary processes, photoreceptors, outer plexiform layer and ganglion cell layer. The P2Y 6 presented almost an identical distribution as the P2Y 4 receptor. The P2Y 11 was also detectable in the retinal pigmented epithelium. The detailed distribution of the receptors clearly supports the recent findings indicating the relevant role of nucleotides in the ocular function.
Progress in Retinal and Eye Research, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Progress in Retinal and Eye Research, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Pharmacology & Therapeutics, 2008
The eye is the sense organ that permits the detection of light owing to the existence of a sophis... more The eye is the sense organ that permits the detection of light owing to the existence of a sophisticated neuronal array, called the retina, which is responsive to photons. The correct functioning of this complex system requires the coordination of several intraocular structures that ultimately permit the perfect focusing of images on the neural retina. Light has to pass through different media: the tear, the cornea, aqueous humour, lens, and vitreous humour before it reaches the retina. Moreover, the composition and structure of some of these media can change due to several physiological mechanisms. Nucleotides are active components of the humours bathing relevant ocular structures. The tear contains nucleotides and dinucleotides that control the process of tearing, wound healing and protects of superficial infections. In the inner eye, the aqueous humour also presents a collection of mono and dinucleotides that affect pupil contraction, aqueous humour production and accommodation. Behind the lens and between this structure and the retina the vitreous humour can modify the physiology of the retinal cells, mostly the ganglion cells. By investigating the actions of nucleotides and dinucleotide present in the ocular humours we will be able not only to understand the functioning of the ocular structures but also to develop new pharmacological therapies for pathologies such as dry eye, glaucoma or retinal detachment.
Pharmacology & Therapeutics, 2008
The eye is the sense organ that permits the detection of light owing to the existence of a sophis... more The eye is the sense organ that permits the detection of light owing to the existence of a sophisticated neuronal array, called the retina, which is responsive to photons. The correct functioning of this complex system requires the coordination of several intraocular structures that ultimately permit the perfect focusing of images on the neural retina. Light has to pass through different media: the tear, the cornea, aqueous humour, lens, and vitreous humour before it reaches the retina. Moreover, the composition and structure of some of these media can change due to several physiological mechanisms. Nucleotides are active components of the humours bathing relevant ocular structures. The tear contains nucleotides and dinucleotides that control the process of tearing, wound healing and protects of superficial infections. In the inner eye, the aqueous humour also presents a collection of mono and dinucleotides that affect pupil contraction, aqueous humour production and accommodation. Behind the lens and between this structure and the retina the vitreous humour can modify the physiology of the retinal cells, mostly the ganglion cells. By investigating the actions of nucleotides and dinucleotide present in the ocular humours we will be able not only to understand the functioning of the ocular structures but also to develop new pharmacological therapies for pathologies such as dry eye, glaucoma or retinal detachment.
Neuroscience Research Communications, 1998
The retina is a complex network of cells and neurotransmitters that function as a light-detecting... more The retina is a complex network of cells and neurotransmitters that function as a light-detecting array and as a signal-processor system. Apart from the neurotransmitters involved in retinal neurotransmission, other substances such as adenosine and ATP, are emerging as important co-transmitters or modulators in this part of the eye. These compounds are naturally occurring purines, which exert their action by means of specific receptors. ATP acts on two main types of receptors, P2X (ionotropic) and P2Y (metabotropic),
Neuroscience Research Communications, 1998
The retina is a complex network of cells and neurotransmitters that function as a light-detecting... more The retina is a complex network of cells and neurotransmitters that function as a light-detecting array and as a signal-processor system. Apart from the neurotransmitters involved in retinal neurotransmission, other substances such as adenosine and ATP, are emerging as important co-transmitters or modulators in this part of the eye. These compounds are naturally occurring purines, which exert their action by means of specific receptors. ATP acts on two main types of receptors, P2X (ionotropic) and P2Y (metabotropic),
Investigative Ophthalmology & Visual Science, 2008
Investigative Ophthalmology & Visual Science, 2006
Investigative Ophthalmology & Visual Science, 2006
Drug News Perspectives, Apr 1, 2008
Dry eye is a multifactorial disease of the tears and the ocular surface that manifests with a wid... more Dry eye is a multifactorial disease of the tears and the ocular surface that manifests with a wide variety of signs and symptoms. It is prevalent in about 33% of the population worldwide. Due to the importance of the pathology, new tests, drugs and technologies have been developed to assist the diagnosis, management and follow-up of the disease. Current available therapies try to alleviate symptoms and to reduce signs in order to restore the ocular surface. Depending on the etiology of the pathology it is possible to use lubricants, secretagogues, biological tear substitutes or antiinflammatory drugs, either independently or combined. Nowadays, the therapies under clinical trial are devoted to stimulating tear components (e.g., diquafosol, a P2Y receptor agonist), or mucin secretion (e.g., rebamipide, an amino acid analogue of quinolinone). Others include gefarnate, a water-insoluble terpene fatty acid that contributes to restoring mucins on the ocular surface, or cevimeline, an oral cholinergic agonist that reduces the symptoms associated with dry eye. Other potential compounds described in patents are in a lower phase of drug development. These compounds come from different families of therapies, and among others, can be found in the form of steroidal and nonsteroidal antiinflammatory agents, vitamins A and D, neurotransmitters and neuropeptides.Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.
European Journal of Pharmacology, Jan 28, 2008
Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-dipho... more Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-diphosphate, UDP, for modulating IOP in New Zealand white rabbits. Uridine 5′ diphosphate, UDP, reduced IOP by 82.9 ± 2.6% compared to control. Dose-response analysis demonstrated a concentration dependent pattern which presented a pD 2 value of 7.57 ± 1.45, equivalent to an EC 50 of 26.91 nM. Of all the tested P2 receptor antagonists, suramin, pyridoxalphosphate-6-azophenyl-2, 4-disulfonic acid (PPADS) and Reactive Blue 2 (RB-2), only the last two were able to reverse the action triggered by UDP. Altogether, UDP acting probably on P2Y 6 receptors present on the ciliary processes, can reduce intraocular pressure, indicating that this substance may be used for the treatment of ocular hypertension and glaucoma.
European Journal of Pharmacology, Jan 28, 2008
Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-dipho... more Nucleotides can modify intraocular pressure (IOP). We have tested the ability of uridine-5′-diphosphate, UDP, for modulating IOP in New Zealand white rabbits. Uridine 5′ diphosphate, UDP, reduced IOP by 82.9 ± 2.6% compared to control. Dose-response analysis demonstrated a concentration dependent pattern which presented a pD 2 value of 7.57 ± 1.45, equivalent to an EC 50 of 26.91 nM. Of all the tested P2 receptor antagonists, suramin, pyridoxalphosphate-6-azophenyl-2, 4-disulfonic acid (PPADS) and Reactive Blue 2 (RB-2), only the last two were able to reverse the action triggered by UDP. Altogether, UDP acting probably on P2Y 6 receptors present on the ciliary processes, can reduce intraocular pressure, indicating that this substance may be used for the treatment of ocular hypertension and glaucoma.
Progress in Retinal and Eye Research, Nov 30, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Progress in Retinal and Eye Research, Nov 30, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Archivos de la Sociedad Española de Oftalmología, 2007
Archivos de la Sociedad Española de Oftalmología, 2007
Acta Ophthalmologica, 2014
Purpose: To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to... more Purpose: To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to estimate the ocular surface changes associated with congenital aniridia compared to normal individuals. Methods: Fifteen patients diagnosed with congenital aniridia and a control group of forty volunteers were studied. Tears were collected to quantify the levels of diadenosine polyphosphates Ap 4 A and Ap 5 A by high-performance liquid chromatography (H.P.L.C). Break-up time (BUT), corneal staining, McMonnies questionnaire and the Schirmer I test were applied to both groups. Results: Dinucleotides in congenital aniridia patients were higher than in control subjects. For the congenital aniridia group, under 15 years old, the values were 0.77 AE 0.01 lM and 0.17 AE 0.02 lM for Ap 4 A and Ap 5 A, respectively. The group aged from 15 to 40 years old provided concentrations of 4.37 AE 0.97 lM and 0.46 AE 0.05 lM for Ap 4 A and Ap 5 A, the group over 40 gave concentrations of 11.17 AE 5.53 lM and 0.68 AE 0.17 lM for Ap 4 A and Ap 5 A. Dinucleotide concentrations increased with age, being statistically significant different among the three age groups (p < 0.05). Congenital aniridia patients showed a normal tear secretion and no dry eye McMonnies scores, except for the group over 40 years old. BUT values decreased and corneal staining increased with age and correlated with the levels of diadenosine polyphosphates (p < 0.05). Conclusions: The levels of dinucleotides in tears increase in aniridia patients compared with healthy subjects, and they seem to be related with the progression of corneal disorders in aniridia patients, both of which increase with ageing.
Acta Ophthalmologica, 2014
To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to estimate... more To quantify diadenosine polyphosphate levels in tears of congenital aniridia patients to estimate the ocular surface changes associated with congenital aniridia compared to normal individuals. Fifteen patients diagnosed with congenital aniridia and a control group of forty volunteers were studied. Tears were collected to quantify the levels of diadenosine polyphosphates Ap4 A and Ap5 A by high-performance liquid chromatography (H.P.L.C). Break-up time (BUT), corneal staining, McMonnies questionnaire and the Schirmer I test were applied to both groups. Dinucleotides in congenital aniridia patients were higher than in control subjects. For the congenital aniridia group, under 15 years old, the values were 0.77 ± 0.01 μm and 0.17 ± 0.02 μm for Ap4 A and Ap5 A, respectively. The group aged from 15 to 40 years old provided concentrations of 4.37 ± 0.97 μm and 0.46 ± 0.05 μm for Ap4 A and Ap5 A, the group over 40 gave concentrations of 11.17 ± 5.53 μm and 0.68 ± 0.17 μm for Ap4 A and Ap5 A. Dinucleotide concentrations increased with age, being statistically significant different among the three age groups (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Congenital aniridia patients showed a normal tear secretion and no dry eye McMonnies scores, except for the group over 40 years old. BUT values decreased and corneal staining increased with age and correlated with the levels of diadenosine polyphosphates (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The levels of dinucleotides in tears increase in aniridia patients compared with healthy subjects, and they seem to be related with the progression of corneal disorders in aniridia patients, both of which increase with ageing.
Purinergic Signalling, 2004
Nucleotides present an important role in ocular physiology, which has been demonstrated by recent... more Nucleotides present an important role in ocular physiology, which has been demonstrated by recent works that indicate their involvement in many ocular processes. P2Y are important among P2 receptors since they can control tear production, corneal wound healing, aqueous humour dynamics and retinal physiology. Commercial antibodies have allowed us to investigate the distribution of P2Y receptors in the cornea, anterior and posterior chamber of the eye and retina. The P2Y 1 receptor was present mainly in cornea, ciliary processes, and trabecular meshwork. The P2Y 2 receptors were present in cornea, ciliary processes and retinal pigmented epithelium. P2Y 4 was present in cornea, ciliary processes, photoreceptors, outer plexiform layer and ganglion cell layer. The P2Y 6 presented almost an identical distribution as the P2Y 4 receptor. The P2Y 11 was also detectable in the retinal pigmented epithelium. The detailed distribution of the receptors clearly supports the recent findings indicating the relevant role of nucleotides in the ocular function.
Progress in Retinal and Eye Research, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Progress in Retinal and Eye Research, 2007
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological... more Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Pharmacology & Therapeutics, 2008
The eye is the sense organ that permits the detection of light owing to the existence of a sophis... more The eye is the sense organ that permits the detection of light owing to the existence of a sophisticated neuronal array, called the retina, which is responsive to photons. The correct functioning of this complex system requires the coordination of several intraocular structures that ultimately permit the perfect focusing of images on the neural retina. Light has to pass through different media: the tear, the cornea, aqueous humour, lens, and vitreous humour before it reaches the retina. Moreover, the composition and structure of some of these media can change due to several physiological mechanisms. Nucleotides are active components of the humours bathing relevant ocular structures. The tear contains nucleotides and dinucleotides that control the process of tearing, wound healing and protects of superficial infections. In the inner eye, the aqueous humour also presents a collection of mono and dinucleotides that affect pupil contraction, aqueous humour production and accommodation. Behind the lens and between this structure and the retina the vitreous humour can modify the physiology of the retinal cells, mostly the ganglion cells. By investigating the actions of nucleotides and dinucleotide present in the ocular humours we will be able not only to understand the functioning of the ocular structures but also to develop new pharmacological therapies for pathologies such as dry eye, glaucoma or retinal detachment.
Pharmacology & Therapeutics, 2008
The eye is the sense organ that permits the detection of light owing to the existence of a sophis... more The eye is the sense organ that permits the detection of light owing to the existence of a sophisticated neuronal array, called the retina, which is responsive to photons. The correct functioning of this complex system requires the coordination of several intraocular structures that ultimately permit the perfect focusing of images on the neural retina. Light has to pass through different media: the tear, the cornea, aqueous humour, lens, and vitreous humour before it reaches the retina. Moreover, the composition and structure of some of these media can change due to several physiological mechanisms. Nucleotides are active components of the humours bathing relevant ocular structures. The tear contains nucleotides and dinucleotides that control the process of tearing, wound healing and protects of superficial infections. In the inner eye, the aqueous humour also presents a collection of mono and dinucleotides that affect pupil contraction, aqueous humour production and accommodation. Behind the lens and between this structure and the retina the vitreous humour can modify the physiology of the retinal cells, mostly the ganglion cells. By investigating the actions of nucleotides and dinucleotide present in the ocular humours we will be able not only to understand the functioning of the ocular structures but also to develop new pharmacological therapies for pathologies such as dry eye, glaucoma or retinal detachment.
Neuroscience Research Communications, 1998
The retina is a complex network of cells and neurotransmitters that function as a light-detecting... more The retina is a complex network of cells and neurotransmitters that function as a light-detecting array and as a signal-processor system. Apart from the neurotransmitters involved in retinal neurotransmission, other substances such as adenosine and ATP, are emerging as important co-transmitters or modulators in this part of the eye. These compounds are naturally occurring purines, which exert their action by means of specific receptors. ATP acts on two main types of receptors, P2X (ionotropic) and P2Y (metabotropic),
Neuroscience Research Communications, 1998
The retina is a complex network of cells and neurotransmitters that function as a light-detecting... more The retina is a complex network of cells and neurotransmitters that function as a light-detecting array and as a signal-processor system. Apart from the neurotransmitters involved in retinal neurotransmission, other substances such as adenosine and ATP, are emerging as important co-transmitters or modulators in this part of the eye. These compounds are naturally occurring purines, which exert their action by means of specific receptors. ATP acts on two main types of receptors, P2X (ionotropic) and P2Y (metabotropic),
Investigative Ophthalmology & Visual Science, 2008
Investigative Ophthalmology & Visual Science, 2006
Investigative Ophthalmology & Visual Science, 2006