E. Gabison - Academia.edu (original) (raw)

Papers by E. Gabison

Research paper thumbnail of 509 Qualité de vie et kératoconjonctivite vernale

Journal Français d'Ophtalmologie, 2007

Research paper thumbnail of Modified Deep Anterior Lamellar Keratoplasty in the Management of Small and Large Epithelialized Descemetoceles

Cornea, 2011

Purpose: Descemetocele is a severe complication of corneal ulceration associated with a high risk... more Purpose: Descemetocele is a severe complication of corneal ulceration associated with a high risk of perforation. We describe a modified air-assisted deep anterior lamellar keratoplasty (DALK) technique for the surgical management of small and large epithelialized descemetoceles. Methods: Two representative cases are presented, one with a small (2 mm) and one with a large (4 mm) descemetocele. In both cases, the air-assisted lamellar dissection allowed a superficial keratectomy and access to the Descemet membrane. Viscoelastic was then directly injected through the stromal hole to separate the Descemet membrane from the posterior stroma, thereby allowing its complete removal. Results: DALK was successfully performed using this modified airassisted DALK technique. Visual acuity improved from counting fingers and hand motion to 20/40 and was maintained for at least 1 year after surgery. Conclusions: These cases demonstrate that the modified airassisted DALK technique may be proposed for the management of small and large descemetoceles, allowing both tectonic and visual rehabilitation.

Research paper thumbnail of Efficacy of azithromycin 1.5% eye drops in childhood ocular rosacea with phlyctenular blepharokeratoconjunctivitis

Journal of ophthalmic inflammation and infection, Jan 22, 2013

The purpose of this study is to report the efficacy of azithromycin 1.5% eye drops in children wi... more The purpose of this study is to report the efficacy of azithromycin 1.5% eye drops in children with ocular rosacea and phlyctenular blepharokeratoconjunctivitis. This retrospective study from January 2009 to March 2010 included 16 children treated with lid hygiene plus azithromycin 1.5% eye drops (Azyter®): 3-day treatments (1 drop twice a day) every 10 days, reduced based on efficacy to one treatment every 15 days and then to one treatment per month. Nineteen eyes of six boys and ten girls, aged 4 to 16 years (mean, 9.3 ± 4.0) were included. The disease was previously resistant to lid hygiene (all the patients), oral erythromycin (one patient), and intermittent topical steroids (six patients). The median duration of each phase of azithromycin treatment (i.e., three, two, and one treatments per month) was 2 months. Ocular inflammation was controlled by azithromycin alone in 15 patients. In one uncontrolled case, cyclosporine 2% eye drops was added at month 5. Bulbar conjunctival hyp...

Research paper thumbnail of Late corneal perforation after photorefractive keratectomy associated with topical diclofenac

Ophthalmology, 2003

ObjectiveTo report a case of a 50-year-old man who was initially seen with a corneal perforation ... more ObjectiveTo report a case of a 50-year-old man who was initially seen with a corneal perforation in his right eye 2 months after a photorefractive keratectomy (PRK) procedure and to discuss the roles of topical diclofenac and matrix metalloproteinases (MMPs).

Research paper thumbnail of Efficacité de la ciclosporine A en collyre à 2 % en tant qu’épargneur de corticoïdes dans le traitement de la kératoconjonctivite vernale corticodépendante

Journal Français d'Ophtalmologie, 2007

ABSTRACT Introduction Vernal keratoconjunctivitis (VKC) is responsible for severe conjunctival an... more ABSTRACT Introduction Vernal keratoconjunctivitis (VKC) is responsible for severe conjunctival and corneal inflammation that often requires topical steroids. Steroid dependency is not rare and can lead to unacceptable complications. The aim of this study was to analyze the efficacy of 2% cyclosporine eye drops (CsA) as a steroid-sparing agent in steroid-dependent VKC. Patients and methods In this noncomparative interventional case series, 18 steroid-dependent VKC patients (17 males, 1 female; mean age, 13 years old) received 2% CsA qid. Topical steroids were associated at decreasing dosage for 1 week and stopped if possible. Efficacy was graded at 1 and 3 months on symptoms, signs and steroid use. Local and systemic tolerability (cyclosporinemia, creatininemia) was also assessed. Results After 1 month, inflammation was controlled without steroids in 11 cases (61%). Low-dose steroids were still necessary to control the disease in four cases (22%). In three cases (17%), the disease was not controlled despite high-dose steroids. At 3 months, results were similar. All patients whose inflammation was partially controlled or not controlled by CsA had active extraocular atopic diseases. Local and systemic tolerability was excellent. Conclusions Topical 2% cyclosporine is inconstantly effective in steroid-dependent VKC. However, this treatment allows for a partial or total reduction of steroids in most cases.

Research paper thumbnail of Sclérites : quand évoquer une pathologie systémique ?

Journal Français d'Ophtalmologie, 2010

Scleritis is typically a severe painful inflammatory disorder of the eye. This process may involv... more Scleritis is typically a severe painful inflammatory disorder of the eye. This process may involve the sclera but also the cornea, adjacent episclera, and underlying uvea and therefore threaten vision. Careful clinical history taking, detailed ocular examination, appropriate investigation for systemic disease, and timely intervention with the use of immunosuppressive drugs when necessary has improved the long-term outcome of patients with scleritis.

Research paper thumbnail of 331 Greffes endothélio-descemétiques par DSAEK : résultats à un an dans la dystrophie de Fuchs

Journal Français d'Ophtalmologie, 2008

Research paper thumbnail of 332 Efficacité du tacrolimus pommade à 0,03 % en application palpébrale cutanée sur la kératoconjonctivite atopique

Journal Français d'Ophtalmologie, 2007

Research paper thumbnail of 227 Kératite en archipel : variante clinique de récurrence herpétique ?

Journal Français d'Ophtalmologie, 2007

Research paper thumbnail of 398 Atteintes ophtalmologiques de la maladie de Fabry

Journal Français d'Ophtalmologie, 2009

Research paper thumbnail of Topical Cyclosporine A in Severe Steroid-Dependent Childhood Phlyctenular Keratoconjunctivitis

American Journal of Ophthalmology, 2006

To assess the efficacy of topical cyclosporine A (CsA) in children with phlyctenular keratoconjun... more To assess the efficacy of topical cyclosporine A (CsA) in children with phlyctenular keratoconjunctivitis associated with severe steroid-dependent corneal inflammation. Prospective, noncomparative, interventional case series. patients: Children with phlyctenular keratoconjunctivitis associated with severe steroid-dependent corneal inflammation and not responding to oral antibiotics (cyclines or erythromycin). intervention: Topical CsA 2% four times daily, initially combined with topical dexamethasone for the first week. main outcome measures: Efficacy was judged by the patients (symptoms and ocular redness) and by the ophthalmologist (ocular redness and corneal inflammation). The patients were monitored for adverse effects, and cyclosporinemia was determined every 3 months. We studied 11 children (13 eyes) with a mean age of 9 years (range, 4 to 15 years). Inflammation was controlled in all the eyes within 14 days. Inflammation did not recur during CsA monotherapy, during a mean follow-up of 12 +/- 8 months (range, 6 to 31 months). CsA therapy was stopped in eight patients (10 eyes) after a mean treatment duration of 13 +/- 9 months (range, 6 to 31 months), and no recurrences occurred during 10 +/- 3 months of follow-up (range, 6 to 12 months). Local tolerance of CsA was good. None of the patients had detectable CsA blood levels. CsA was withdrawn in one case after 6 months, because of generalized skin rash. Long-term topical CsA 2% therapy is safe and effective in children with phlyctenular keratoconjunctivitis associated with severe steroid-dependent corneal inflammation.

Research paper thumbnail of Efficacy of gas permeable scleral lenses in refractory severe dry eye syndrome

Acta Ophthalmologica, 2012

ABSTRACT Purpose Modern scleral lenses have shown their efficacy in severe ocular surface disease... more ABSTRACT Purpose Modern scleral lenses have shown their efficacy in severe ocular surface diseases such as Stevens-Johnson syndrome. Their geometry allows hydration and protection of the cornea and of the limbus. This study determined the efficacy of modern scleral contact lenses in severe eye dry syndrome. Methods A retrospective single-center study was conducted in patients with severe refractory dry eye syndrome, who were fitted with SPOT® scleral lenses (LAO, Thonon, France). At inclusion and after 3 months of daily wear, the following parameters were assessed: Ocular Surface Disease Index (OSDI) score, NEI Visual Function Questionnaire-25 composite score (NEI VFQ-25), best-corrected visual acuity, slit lamp examination, number of associated drugs and tolerability. Results The files of 10 patients (9 women and 1 man) with a mean age of 58.4 years (40-80 years), were reviewed. Dry eye was related to Sjögren syndrome (6 patients), ocular cicatricial pemphigoid (3 patients) and graft versus host disease (1 patient). Lens fitting failed in 1 case. Improvement of quality of life scores (OSDI and NEI NFQ-25) was remarkable in seven patients out of the nine fitted patients. Mean OSDI and NEI VFQ-25 scores improved from 73.5±16.8 to 35±24.2 (p=0.002) and from 49.0±21.0 to 70.5±18.4 (p=0.045), respectively. Best corrected visual acuity improved by 3.2±4.3 Snellen lines. Mean follow-up was 12.6±3.8 months. No serious adverse events attributable to the scleral lenses occurred. Conclusion Scleral lenses are a promising therapeutic in patients with severe refractory dry eye syndrome. The results can be spectacular with a dramatic improvement of patients’ quality of life. Difficulties in manipulation represent the main disadvantage.

Research paper thumbnail of Gene transfer of HSV1-specific meganuclease to the murine cornea

Acta Ophthalmologica, 2012

ABSTRACT Purpose Recombinant Adeno-Associated virus (rAVV) encoding meganucleases specifically de... more ABSTRACT Purpose Recombinant Adeno-Associated virus (rAVV) encoding meganucleases specifically designed to address Herpes simplex virus type 1 (HSV1) reduce HSV1 replication both in vitro and ex-vivo. The main issue of this potential antiviral treatment is the delivery system. To evaluate a vector-free method, we tested an electroporation process to transfer HSV1-specific meganucleases (HSV1-SM) to the murine cornea Methods Corneal gene transfer was achieved by subconjunctival injection (SCI) of recombinant plasmid encoding either GFP (group 1; n=30) or HSV1-SM (group 2; n=12), followed by electroporation. Mice were sacrified at day (D)1, 3, 7, 13, 35 (group 1) and at D13 and 35 (group 2). Control group consisted in SCI w/o electroporation. Corneal samples were analyzed for the expression of transcripts encoding GFP and HSV1-SM using real time PCR. The results were compared to those obtained following SCI of rAAV encoding either GFP or HSV1-SM Results For HSV1-SM, SCI plus electroporation induced a stronger expression than SCI alone at D13. In group 1, the expression of GFP transcripts decreased from D1 to D35. However, until D13, their levels of expression were higher than those obtained with the rAAV method (p

Research paper thumbnail of HSV1-specific meganuclease may reduce ocular infection in a mouse model of herpes keratitis

Acta Ophthalmologica, 2012

ABSTRACT Purpose Current anti-viral treatments of Herpes simplex virus type 1 (HSV1) inhibit the ... more ABSTRACT Purpose Current anti-viral treatments of Herpes simplex virus type 1 (HSV1) inhibit the viral replication but do not impair the latent form of the virus. This could be addressed by rare cutting endonucleases, such as meganucleases. The aim of this study was to demonstrate the antiviral activity of a HSV1-specific meganuclease in a mouse model of herpes keratitis. Methods Three weeks after bilateral subconjunctival inoculation of recombinant associated-adenovirus (rAAV) encoding either a HSV1-specific meganuclease or a reporter gene (GFP), both cornea of mice were inoculated with a wild-type HSV1 strain. Mice were sacrificed 6 or 28 days later and corneas were analyzed for the presence of HSV1 genome and viral transcripts. Results At 6 dpi, there was no clinical difference in the rate of acute herpetic keratitis, but the amounts of viral products were lower in mice treated with meganuclease-encoding rAAV. At 28 dpi (stage of HSV1 latency), the rate of clear cornea was more important in the mice treated with meganuclease (p = 0.03), and the amounts of viral genome and transcripts were significantly less important (p<0.01. Conclusion The transduction of HSV1-specific meganucleases in the ocular tissues by means of a subconjunctival inoculation of r-AAV is associated with an improvement of corneal recovery, and a reduction in the viral load and replication in the cornea. These results suggest that specific meganucleases could be qualified as a new class of antiviral agent, with the potential to address replicative as well as latent viral DNA. Commercial interest

Research paper thumbnail of Direct epithelial–stromal interaction in corneal wound healing: Role of EMMPRIN/CD147 in MMPs induction and beyond

Progress in Retinal and Eye Research, 2009

In the cornea, the epithelium and the underlying stroma are separated by the basement membrane an... more In the cornea, the epithelium and the underlying stroma are separated by the basement membrane and Bowman's layer. The disruption of these anatomical barriers during wound healing represents a key step which initiates tissue remodeling through the modification of the epithelial-stromal interactions (ESI). Diffusible cytokines are generally viewed as central modulators in the bidirectional communication between these epithelial and stromal compartments and their implication in all stages of the wound healing process has been an active area of research for many years. Our studies which aimed to explore mechanisms of matrix degradation in pathological corneal wound healing have shown that EMMPRIN, a glycoprotein expressed on corneal epithelial cell surface, can induce matrix metalloproteinase (MMP) production and myofibroblasts differentiation after direct interaction with corneal fibroblasts. EMMPRIN appears therefore as a potential mediator of ESI by direct cell-cell contact which represents a new mechanism for dysregulated MMPs' induction observed in corneal ulcerations. These direct epithelial-stromal interactions (direct-ESI) can occur when delayed epithelial healing prevents regeneration of the basement membrane and allows the two cell types to come into close proximity. We propose that prevention of these interactions through inhibition of EMMPRIN may represent a promising therapeutic strategy in the inhibition of MMP induction in ulceration.

Research paper thumbnail of 509 Qualité de vie et kératoconjonctivite vernale

Journal Français d'Ophtalmologie, 2007

Research paper thumbnail of Modified Deep Anterior Lamellar Keratoplasty in the Management of Small and Large Epithelialized Descemetoceles

Cornea, 2011

Purpose: Descemetocele is a severe complication of corneal ulceration associated with a high risk... more Purpose: Descemetocele is a severe complication of corneal ulceration associated with a high risk of perforation. We describe a modified air-assisted deep anterior lamellar keratoplasty (DALK) technique for the surgical management of small and large epithelialized descemetoceles. Methods: Two representative cases are presented, one with a small (2 mm) and one with a large (4 mm) descemetocele. In both cases, the air-assisted lamellar dissection allowed a superficial keratectomy and access to the Descemet membrane. Viscoelastic was then directly injected through the stromal hole to separate the Descemet membrane from the posterior stroma, thereby allowing its complete removal. Results: DALK was successfully performed using this modified airassisted DALK technique. Visual acuity improved from counting fingers and hand motion to 20/40 and was maintained for at least 1 year after surgery. Conclusions: These cases demonstrate that the modified airassisted DALK technique may be proposed for the management of small and large descemetoceles, allowing both tectonic and visual rehabilitation.

Research paper thumbnail of Efficacy of azithromycin 1.5% eye drops in childhood ocular rosacea with phlyctenular blepharokeratoconjunctivitis

Journal of ophthalmic inflammation and infection, Jan 22, 2013

The purpose of this study is to report the efficacy of azithromycin 1.5% eye drops in children wi... more The purpose of this study is to report the efficacy of azithromycin 1.5% eye drops in children with ocular rosacea and phlyctenular blepharokeratoconjunctivitis. This retrospective study from January 2009 to March 2010 included 16 children treated with lid hygiene plus azithromycin 1.5% eye drops (Azyter®): 3-day treatments (1 drop twice a day) every 10 days, reduced based on efficacy to one treatment every 15 days and then to one treatment per month. Nineteen eyes of six boys and ten girls, aged 4 to 16 years (mean, 9.3 ± 4.0) were included. The disease was previously resistant to lid hygiene (all the patients), oral erythromycin (one patient), and intermittent topical steroids (six patients). The median duration of each phase of azithromycin treatment (i.e., three, two, and one treatments per month) was 2 months. Ocular inflammation was controlled by azithromycin alone in 15 patients. In one uncontrolled case, cyclosporine 2% eye drops was added at month 5. Bulbar conjunctival hyp...

Research paper thumbnail of Late corneal perforation after photorefractive keratectomy associated with topical diclofenac

Ophthalmology, 2003

ObjectiveTo report a case of a 50-year-old man who was initially seen with a corneal perforation ... more ObjectiveTo report a case of a 50-year-old man who was initially seen with a corneal perforation in his right eye 2 months after a photorefractive keratectomy (PRK) procedure and to discuss the roles of topical diclofenac and matrix metalloproteinases (MMPs).

Research paper thumbnail of Efficacité de la ciclosporine A en collyre à 2 % en tant qu’épargneur de corticoïdes dans le traitement de la kératoconjonctivite vernale corticodépendante

Journal Français d'Ophtalmologie, 2007

ABSTRACT Introduction Vernal keratoconjunctivitis (VKC) is responsible for severe conjunctival an... more ABSTRACT Introduction Vernal keratoconjunctivitis (VKC) is responsible for severe conjunctival and corneal inflammation that often requires topical steroids. Steroid dependency is not rare and can lead to unacceptable complications. The aim of this study was to analyze the efficacy of 2% cyclosporine eye drops (CsA) as a steroid-sparing agent in steroid-dependent VKC. Patients and methods In this noncomparative interventional case series, 18 steroid-dependent VKC patients (17 males, 1 female; mean age, 13 years old) received 2% CsA qid. Topical steroids were associated at decreasing dosage for 1 week and stopped if possible. Efficacy was graded at 1 and 3 months on symptoms, signs and steroid use. Local and systemic tolerability (cyclosporinemia, creatininemia) was also assessed. Results After 1 month, inflammation was controlled without steroids in 11 cases (61%). Low-dose steroids were still necessary to control the disease in four cases (22%). In three cases (17%), the disease was not controlled despite high-dose steroids. At 3 months, results were similar. All patients whose inflammation was partially controlled or not controlled by CsA had active extraocular atopic diseases. Local and systemic tolerability was excellent. Conclusions Topical 2% cyclosporine is inconstantly effective in steroid-dependent VKC. However, this treatment allows for a partial or total reduction of steroids in most cases.

Research paper thumbnail of Sclérites : quand évoquer une pathologie systémique ?

Journal Français d'Ophtalmologie, 2010

Scleritis is typically a severe painful inflammatory disorder of the eye. This process may involv... more Scleritis is typically a severe painful inflammatory disorder of the eye. This process may involve the sclera but also the cornea, adjacent episclera, and underlying uvea and therefore threaten vision. Careful clinical history taking, detailed ocular examination, appropriate investigation for systemic disease, and timely intervention with the use of immunosuppressive drugs when necessary has improved the long-term outcome of patients with scleritis.

Research paper thumbnail of 331 Greffes endothélio-descemétiques par DSAEK : résultats à un an dans la dystrophie de Fuchs

Journal Français d'Ophtalmologie, 2008

Research paper thumbnail of 332 Efficacité du tacrolimus pommade à 0,03 % en application palpébrale cutanée sur la kératoconjonctivite atopique

Journal Français d'Ophtalmologie, 2007

Research paper thumbnail of 227 Kératite en archipel : variante clinique de récurrence herpétique ?

Journal Français d'Ophtalmologie, 2007

Research paper thumbnail of 398 Atteintes ophtalmologiques de la maladie de Fabry

Journal Français d'Ophtalmologie, 2009

Research paper thumbnail of Topical Cyclosporine A in Severe Steroid-Dependent Childhood Phlyctenular Keratoconjunctivitis

American Journal of Ophthalmology, 2006

To assess the efficacy of topical cyclosporine A (CsA) in children with phlyctenular keratoconjun... more To assess the efficacy of topical cyclosporine A (CsA) in children with phlyctenular keratoconjunctivitis associated with severe steroid-dependent corneal inflammation. Prospective, noncomparative, interventional case series. patients: Children with phlyctenular keratoconjunctivitis associated with severe steroid-dependent corneal inflammation and not responding to oral antibiotics (cyclines or erythromycin). intervention: Topical CsA 2% four times daily, initially combined with topical dexamethasone for the first week. main outcome measures: Efficacy was judged by the patients (symptoms and ocular redness) and by the ophthalmologist (ocular redness and corneal inflammation). The patients were monitored for adverse effects, and cyclosporinemia was determined every 3 months. We studied 11 children (13 eyes) with a mean age of 9 years (range, 4 to 15 years). Inflammation was controlled in all the eyes within 14 days. Inflammation did not recur during CsA monotherapy, during a mean follow-up of 12 +/- 8 months (range, 6 to 31 months). CsA therapy was stopped in eight patients (10 eyes) after a mean treatment duration of 13 +/- 9 months (range, 6 to 31 months), and no recurrences occurred during 10 +/- 3 months of follow-up (range, 6 to 12 months). Local tolerance of CsA was good. None of the patients had detectable CsA blood levels. CsA was withdrawn in one case after 6 months, because of generalized skin rash. Long-term topical CsA 2% therapy is safe and effective in children with phlyctenular keratoconjunctivitis associated with severe steroid-dependent corneal inflammation.

Research paper thumbnail of Efficacy of gas permeable scleral lenses in refractory severe dry eye syndrome

Acta Ophthalmologica, 2012

ABSTRACT Purpose Modern scleral lenses have shown their efficacy in severe ocular surface disease... more ABSTRACT Purpose Modern scleral lenses have shown their efficacy in severe ocular surface diseases such as Stevens-Johnson syndrome. Their geometry allows hydration and protection of the cornea and of the limbus. This study determined the efficacy of modern scleral contact lenses in severe eye dry syndrome. Methods A retrospective single-center study was conducted in patients with severe refractory dry eye syndrome, who were fitted with SPOT® scleral lenses (LAO, Thonon, France). At inclusion and after 3 months of daily wear, the following parameters were assessed: Ocular Surface Disease Index (OSDI) score, NEI Visual Function Questionnaire-25 composite score (NEI VFQ-25), best-corrected visual acuity, slit lamp examination, number of associated drugs and tolerability. Results The files of 10 patients (9 women and 1 man) with a mean age of 58.4 years (40-80 years), were reviewed. Dry eye was related to Sjögren syndrome (6 patients), ocular cicatricial pemphigoid (3 patients) and graft versus host disease (1 patient). Lens fitting failed in 1 case. Improvement of quality of life scores (OSDI and NEI NFQ-25) was remarkable in seven patients out of the nine fitted patients. Mean OSDI and NEI VFQ-25 scores improved from 73.5±16.8 to 35±24.2 (p=0.002) and from 49.0±21.0 to 70.5±18.4 (p=0.045), respectively. Best corrected visual acuity improved by 3.2±4.3 Snellen lines. Mean follow-up was 12.6±3.8 months. No serious adverse events attributable to the scleral lenses occurred. Conclusion Scleral lenses are a promising therapeutic in patients with severe refractory dry eye syndrome. The results can be spectacular with a dramatic improvement of patients’ quality of life. Difficulties in manipulation represent the main disadvantage.

Research paper thumbnail of Gene transfer of HSV1-specific meganuclease to the murine cornea

Acta Ophthalmologica, 2012

ABSTRACT Purpose Recombinant Adeno-Associated virus (rAVV) encoding meganucleases specifically de... more ABSTRACT Purpose Recombinant Adeno-Associated virus (rAVV) encoding meganucleases specifically designed to address Herpes simplex virus type 1 (HSV1) reduce HSV1 replication both in vitro and ex-vivo. The main issue of this potential antiviral treatment is the delivery system. To evaluate a vector-free method, we tested an electroporation process to transfer HSV1-specific meganucleases (HSV1-SM) to the murine cornea Methods Corneal gene transfer was achieved by subconjunctival injection (SCI) of recombinant plasmid encoding either GFP (group 1; n=30) or HSV1-SM (group 2; n=12), followed by electroporation. Mice were sacrified at day (D)1, 3, 7, 13, 35 (group 1) and at D13 and 35 (group 2). Control group consisted in SCI w/o electroporation. Corneal samples were analyzed for the expression of transcripts encoding GFP and HSV1-SM using real time PCR. The results were compared to those obtained following SCI of rAAV encoding either GFP or HSV1-SM Results For HSV1-SM, SCI plus electroporation induced a stronger expression than SCI alone at D13. In group 1, the expression of GFP transcripts decreased from D1 to D35. However, until D13, their levels of expression were higher than those obtained with the rAAV method (p

Research paper thumbnail of HSV1-specific meganuclease may reduce ocular infection in a mouse model of herpes keratitis

Acta Ophthalmologica, 2012

ABSTRACT Purpose Current anti-viral treatments of Herpes simplex virus type 1 (HSV1) inhibit the ... more ABSTRACT Purpose Current anti-viral treatments of Herpes simplex virus type 1 (HSV1) inhibit the viral replication but do not impair the latent form of the virus. This could be addressed by rare cutting endonucleases, such as meganucleases. The aim of this study was to demonstrate the antiviral activity of a HSV1-specific meganuclease in a mouse model of herpes keratitis. Methods Three weeks after bilateral subconjunctival inoculation of recombinant associated-adenovirus (rAAV) encoding either a HSV1-specific meganuclease or a reporter gene (GFP), both cornea of mice were inoculated with a wild-type HSV1 strain. Mice were sacrificed 6 or 28 days later and corneas were analyzed for the presence of HSV1 genome and viral transcripts. Results At 6 dpi, there was no clinical difference in the rate of acute herpetic keratitis, but the amounts of viral products were lower in mice treated with meganuclease-encoding rAAV. At 28 dpi (stage of HSV1 latency), the rate of clear cornea was more important in the mice treated with meganuclease (p = 0.03), and the amounts of viral genome and transcripts were significantly less important (p<0.01. Conclusion The transduction of HSV1-specific meganucleases in the ocular tissues by means of a subconjunctival inoculation of r-AAV is associated with an improvement of corneal recovery, and a reduction in the viral load and replication in the cornea. These results suggest that specific meganucleases could be qualified as a new class of antiviral agent, with the potential to address replicative as well as latent viral DNA. Commercial interest

Research paper thumbnail of Direct epithelial–stromal interaction in corneal wound healing: Role of EMMPRIN/CD147 in MMPs induction and beyond

Progress in Retinal and Eye Research, 2009

In the cornea, the epithelium and the underlying stroma are separated by the basement membrane an... more In the cornea, the epithelium and the underlying stroma are separated by the basement membrane and Bowman's layer. The disruption of these anatomical barriers during wound healing represents a key step which initiates tissue remodeling through the modification of the epithelial-stromal interactions (ESI). Diffusible cytokines are generally viewed as central modulators in the bidirectional communication between these epithelial and stromal compartments and their implication in all stages of the wound healing process has been an active area of research for many years. Our studies which aimed to explore mechanisms of matrix degradation in pathological corneal wound healing have shown that EMMPRIN, a glycoprotein expressed on corneal epithelial cell surface, can induce matrix metalloproteinase (MMP) production and myofibroblasts differentiation after direct interaction with corneal fibroblasts. EMMPRIN appears therefore as a potential mediator of ESI by direct cell-cell contact which represents a new mechanism for dysregulated MMPs' induction observed in corneal ulcerations. These direct epithelial-stromal interactions (direct-ESI) can occur when delayed epithelial healing prevents regeneration of the basement membrane and allows the two cell types to come into close proximity. We propose that prevention of these interactions through inhibition of EMMPRIN may represent a promising therapeutic strategy in the inhibition of MMP induction in ulceration.