Cindy Hutnik | University of Western Ontario (original) (raw)
Papers by Cindy Hutnik
Investigative Ophthalmology & Visual Science, Apr 30, 2014
Currently she is the President of the Canadian Glaucoma Society, Chair of the Governing Committee... more Currently she is the President of the Canadian Glaucoma Society, Chair of the Governing Committee of the Academic Medical Organization of Southwestern Ontario and a member of the Board of Glaucoma Research Society of Canada. She has a keen interest in the development of novel and/or optimization of existing treatments for patients with glaucoma.
![Research paper thumbnail of Optimal Use of Minimally Invasive Glaucoma Surgery: A Health Technology Assessment [Internet]](https://attachments.academia-assets.com/118373808/thumbnails/1.jpg)
](This report contains a comprehensive review of existing public literature, studies, materials, an... more This report contains a comprehensive review of existing public literature, studies, materials, and other information and documentation (collectively the "source documentation") available to CADTH at the time it was prepared, and it was guided by expert input and advice throughout its preparation. The information in this report is intended to help health care decision-makers, patients, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment in respect to the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this report to ensure that its contents are accurate, complete, and upto-date, CADTH does not make any guarantee to that effect. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or as a result of the use (or misuse) of any information contained in or implied by the information in this report CADTH takes sole responsibility for the final form and content of this report. The statements, conclusions, and views expressed herein do not necessarily represent the view of Health Canada or any provincial or territorial government. Production of this report is made possible through a financial contribution from Health Canada.
Investigative Ophthalmology & Visual Science, Sep 26, 2016
Investigative Ophthalmology & Visual Science, May 1, 2006
The retinoic acid derivative fenretinide (FR) is capable of transdifferentiating cultured retinal... more The retinoic acid derivative fenretinide (FR) is capable of transdifferentiating cultured retinal pigment epithelial (RPE) cells towards a neuronal-like phenotype, but the underlying mechanisms are not understood. To identify genes involved in this process we performed a microarray analysis of RPE cells pre-and post-FR treatment, and observed a marked down-regulation of AnnexinA8 (AnxA8) in transdifferentiated cells. To determine whether AnxA8 plays a role in maintaining RPE cell phenotype we directly manipulated AnxA8 expression in cultured and primary RPE cells using siRNA-mediated gene suppression, and over-expression of AnxA8-GFP in conjunction with exposure to FR. Treatment of RPE cells with AnxA8 siRNA recapitulated exposure to FR, with cell cycle arrest, neuronal transdifferentiation, and concomitant up-regulation of the neuronal markers calretinin and calbindin, as assessed by real-time PCR and immunofluorescence. In contrast, AnxA8 transient over-expression in ARPE-19 cells prevented FR-induced differentiation. Ectopic expression of AnxA8 in AnxA8-depleted cells led to decreased neuronal marker staining, and normal cell growth as judged by phosphohistone H3 staining, cell counting and cleaved caspase-3 levels. These data show that down-regulation of AnxA8 is both necessary and sufficient for neuronal transdifferentiation of RPE cells and reveal an essential role for AnxA8 as a key regulator of RPE phenotype. Retinal pigment epithelial (RPE) cells and the retina are developmentally derived from the same tissue; the optic vesicle neuroectoderm, and throughout life RPE cells perform a variety of functions to support and protect the retina. These include phagocytosis of photoreceptor outer segments 1 , adsorption of free radicals by pigment granules 2 and maintenance of ocular immune privilege by forming the outer blood-retina barrier 3. Another striking feature of RPE cells, in some species, is their capacity to transdifferentiate into precursor cells and regenerate neuronal tissue. Accordingly, in urodele amphibians such as newts, complete retinal regeneration occurs via RPE transdifferentiation following ocular neuronal injury regardless of life stage 4, 5. In mammals, however, the ability of RPE cells to transdifferentiate in vivo is lost during early embryonic development. Therefore, neuronal cell injury, of the type that occurs in neurodegenerative diseases such as retinitis pigmentosa or age-related macular degeneration, usually results in irreversible vision loss 6, 7. However, there is evidence that despite being largely post-mitotic, some mature RPE cells continue to divide 8, 9 mostly in the peripheral retina 10 , as well as during pathological complications following retinal detachment that lead to proliferative vitreoretinopathy 11. In contrast, when cultured ex vivo, RPE cells can be highly proliferative, though this is usually accompanied by substantial de-differentiation manifested as loss of pigment granules, cell polarity and expression of key RPE cell genes such as RPE65 and the Mer tyrosine kinase. Various studies have shown that under suitable conditions, a more authentic RPE cell phenotype can be restored, demonstrating the phenotypic plasticity of these cells in culture 12. Conversely, RPE transdifferentiation can be induced in vitro by basic fibroblast growth factor (bFGF) or retinoic acid (RA) 13-15 , factors known to play a key role in RPE reprogramming during development and retinal regeneration in urodeles 16. In this study, the RA derivative Fenretinide (FR) was used to induce transdifferentiation of RPE cells towards a neuronal-like phenotype as described previously 15, 17. FR exerts its properties in a similar manner to RA; upon
Investigative Ophthalmology & Visual Science, May 14, 2008
Investigative Ophthalmology & Visual Science, Apr 22, 2011
Investigative Ophthalmology & Visual Science, Mar 26, 2012
Investigative Ophthalmology & Visual Science, Apr 30, 2014
Investigative Ophthalmology & Visual Science, Jun 21, 2021
Investigative Ophthalmology & Visual Science, Jul 13, 2018
PLOS ONE, Jul 6, 2015
<p>Funnel plot for pre- and post-operative IOPR% for studies comparing iStent insertion wit... more <p>Funnel plot for pre- and post-operative IOPR% for studies comparing iStent insertion with phacoemulsification versus phacoemulsification as a solo procedure.</p
Investigative Ophthalmology & Visual Science, May 1, 2005
Canadian journal of ophthalmology, Oct 1, 2022
Clinical Ophthalmology, Jul 1, 2019
Purpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells. Methods... more Purpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells. Methods: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA). Results: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs. Conclusions: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.
Current Opinion in Ophthalmology, Feb 1, 1998
Women's Health, Dec 31, 2022
Canadian journal of ophthalmology, Aug 1, 2023
Ophthalmology Glaucoma, Nov 1, 2019
In thyroid eye disease (TED), intraocular pressure (IOP) measurements are taken in both the prima... more In thyroid eye disease (TED), intraocular pressure (IOP) measurements are taken in both the primary and upgaze positions to elicit restrictive muscle disease. The aim of this study was to assess whether the IOP when measured with the eyes in upgaze (the Goldmann applanation tonometer [GAT] head applanating the inferior/peripheral cornea) is similar when compared with the central corneal IOP in upgaze using the Tono-Pen XL. Methods: IOP was measured with the GAT on the central cornea in primary gaze and on the inferior cornea in upgaze. IOP was measured with the Tono-Pen XL in the central cornea in both primary gaze and upgaze. The outcome measure was the difference in IOP readings between the GAT and the Tono-Pen XL for patients with restrictive TED. Results: Fifty-two patients were included in the study; 31 patients with restrictive TED and 21 control patients. In the control group, there was no significant difference in Tono-Pen XL and GAT readings for both primary gaze and upgaze (p ϭ 0.99). Both instruments detected an increase in IOP with upgaze in patients with restrictive TED compared with controls (p ϭ 0.0006). There was no significant difference between the 2 instruments' readings in upgaze for patients with restrictive TED (p ϭ 0.39). Conclusions: Both the GAT and the Tono-Pen XL can be used to establish IOP in patients with restrictive TED.
Investigative Ophthalmology & Visual Science, May 14, 2008
Investigative Ophthalmology & Visual Science, Apr 30, 2014
Currently she is the President of the Canadian Glaucoma Society, Chair of the Governing Committee... more Currently she is the President of the Canadian Glaucoma Society, Chair of the Governing Committee of the Academic Medical Organization of Southwestern Ontario and a member of the Board of Glaucoma Research Society of Canada. She has a keen interest in the development of novel and/or optimization of existing treatments for patients with glaucoma.
This report contains a comprehensive review of existing public literature, studies, materials, an... more This report contains a comprehensive review of existing public literature, studies, materials, and other information and documentation (collectively the "source documentation") available to CADTH at the time it was prepared, and it was guided by expert input and advice throughout its preparation. The information in this report is intended to help health care decision-makers, patients, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment in respect to the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this report to ensure that its contents are accurate, complete, and upto-date, CADTH does not make any guarantee to that effect. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or as a result of the use (or misuse) of any information contained in or implied by the information in this report CADTH takes sole responsibility for the final form and content of this report. The statements, conclusions, and views expressed herein do not necessarily represent the view of Health Canada or any provincial or territorial government. Production of this report is made possible through a financial contribution from Health Canada.
Investigative Ophthalmology & Visual Science, Sep 26, 2016
Investigative Ophthalmology & Visual Science, May 1, 2006
The retinoic acid derivative fenretinide (FR) is capable of transdifferentiating cultured retinal... more The retinoic acid derivative fenretinide (FR) is capable of transdifferentiating cultured retinal pigment epithelial (RPE) cells towards a neuronal-like phenotype, but the underlying mechanisms are not understood. To identify genes involved in this process we performed a microarray analysis of RPE cells pre-and post-FR treatment, and observed a marked down-regulation of AnnexinA8 (AnxA8) in transdifferentiated cells. To determine whether AnxA8 plays a role in maintaining RPE cell phenotype we directly manipulated AnxA8 expression in cultured and primary RPE cells using siRNA-mediated gene suppression, and over-expression of AnxA8-GFP in conjunction with exposure to FR. Treatment of RPE cells with AnxA8 siRNA recapitulated exposure to FR, with cell cycle arrest, neuronal transdifferentiation, and concomitant up-regulation of the neuronal markers calretinin and calbindin, as assessed by real-time PCR and immunofluorescence. In contrast, AnxA8 transient over-expression in ARPE-19 cells prevented FR-induced differentiation. Ectopic expression of AnxA8 in AnxA8-depleted cells led to decreased neuronal marker staining, and normal cell growth as judged by phosphohistone H3 staining, cell counting and cleaved caspase-3 levels. These data show that down-regulation of AnxA8 is both necessary and sufficient for neuronal transdifferentiation of RPE cells and reveal an essential role for AnxA8 as a key regulator of RPE phenotype. Retinal pigment epithelial (RPE) cells and the retina are developmentally derived from the same tissue; the optic vesicle neuroectoderm, and throughout life RPE cells perform a variety of functions to support and protect the retina. These include phagocytosis of photoreceptor outer segments 1 , adsorption of free radicals by pigment granules 2 and maintenance of ocular immune privilege by forming the outer blood-retina barrier 3. Another striking feature of RPE cells, in some species, is their capacity to transdifferentiate into precursor cells and regenerate neuronal tissue. Accordingly, in urodele amphibians such as newts, complete retinal regeneration occurs via RPE transdifferentiation following ocular neuronal injury regardless of life stage 4, 5. In mammals, however, the ability of RPE cells to transdifferentiate in vivo is lost during early embryonic development. Therefore, neuronal cell injury, of the type that occurs in neurodegenerative diseases such as retinitis pigmentosa or age-related macular degeneration, usually results in irreversible vision loss 6, 7. However, there is evidence that despite being largely post-mitotic, some mature RPE cells continue to divide 8, 9 mostly in the peripheral retina 10 , as well as during pathological complications following retinal detachment that lead to proliferative vitreoretinopathy 11. In contrast, when cultured ex vivo, RPE cells can be highly proliferative, though this is usually accompanied by substantial de-differentiation manifested as loss of pigment granules, cell polarity and expression of key RPE cell genes such as RPE65 and the Mer tyrosine kinase. Various studies have shown that under suitable conditions, a more authentic RPE cell phenotype can be restored, demonstrating the phenotypic plasticity of these cells in culture 12. Conversely, RPE transdifferentiation can be induced in vitro by basic fibroblast growth factor (bFGF) or retinoic acid (RA) 13-15 , factors known to play a key role in RPE reprogramming during development and retinal regeneration in urodeles 16. In this study, the RA derivative Fenretinide (FR) was used to induce transdifferentiation of RPE cells towards a neuronal-like phenotype as described previously 15, 17. FR exerts its properties in a similar manner to RA; upon
Investigative Ophthalmology & Visual Science, May 14, 2008
Investigative Ophthalmology & Visual Science, Apr 22, 2011
Investigative Ophthalmology & Visual Science, Mar 26, 2012
Investigative Ophthalmology & Visual Science, Apr 30, 2014
Investigative Ophthalmology & Visual Science, Jun 21, 2021
Investigative Ophthalmology & Visual Science, Jul 13, 2018
PLOS ONE, Jul 6, 2015
<p>Funnel plot for pre- and post-operative IOPR% for studies comparing iStent insertion wit... more <p>Funnel plot for pre- and post-operative IOPR% for studies comparing iStent insertion with phacoemulsification versus phacoemulsification as a solo procedure.</p
Investigative Ophthalmology & Visual Science, May 1, 2005
Canadian journal of ophthalmology, Oct 1, 2022
Clinical Ophthalmology, Jul 1, 2019
Purpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells. Methods... more Purpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells. Methods: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA). Results: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs. Conclusions: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.
Current Opinion in Ophthalmology, Feb 1, 1998
Women's Health, Dec 31, 2022
Canadian journal of ophthalmology, Aug 1, 2023
Ophthalmology Glaucoma, Nov 1, 2019
In thyroid eye disease (TED), intraocular pressure (IOP) measurements are taken in both the prima... more In thyroid eye disease (TED), intraocular pressure (IOP) measurements are taken in both the primary and upgaze positions to elicit restrictive muscle disease. The aim of this study was to assess whether the IOP when measured with the eyes in upgaze (the Goldmann applanation tonometer [GAT] head applanating the inferior/peripheral cornea) is similar when compared with the central corneal IOP in upgaze using the Tono-Pen XL. Methods: IOP was measured with the GAT on the central cornea in primary gaze and on the inferior cornea in upgaze. IOP was measured with the Tono-Pen XL in the central cornea in both primary gaze and upgaze. The outcome measure was the difference in IOP readings between the GAT and the Tono-Pen XL for patients with restrictive TED. Results: Fifty-two patients were included in the study; 31 patients with restrictive TED and 21 control patients. In the control group, there was no significant difference in Tono-Pen XL and GAT readings for both primary gaze and upgaze (p ϭ 0.99). Both instruments detected an increase in IOP with upgaze in patients with restrictive TED compared with controls (p ϭ 0.0006). There was no significant difference between the 2 instruments' readings in upgaze for patients with restrictive TED (p ϭ 0.39). Conclusions: Both the GAT and the Tono-Pen XL can be used to establish IOP in patients with restrictive TED.
Investigative Ophthalmology & Visual Science, May 14, 2008