scholarly journals Intraocular injection of ES cell-derived neural progenitors improve visual function in retinal ganglion cell-depleted mouse models

2017 ◽  
Author(s):  
Mundackal Sivaraman Divya ◽  
Vazhanthodi Abdul Rasheed ◽  
Tiffany Schmidt ◽  
Soundararajan Lalitha ◽  
Samer Hattar ◽  
...  

AbstractRetinal ganglion cells (RGC) transplantation is a promising strategy to restore visual function resulting from irreversible RGC degeneration occurring in glaucoma or inherited optic neuropathies. We previously demonstrated FGF2 induced differentiation of mouse embryonic stem cells (ESC) to RGC lineage, capable of retinal Ganglion Cell Layer (GCL) integration upon transplantation in mice. Here, we evaluated possible improvement of visual function by transplantation of ES cell derived neural progenitors in RGC depleted glaucoma mice models. ESC derived neural progenitors (ES-NP) were transplanted into NMDA (N-Methyl-D-Aspartate) injected, RGC-ablated mouse models and a pre-clinical glaucoma mouse model (DBA/2J) having sustained higher intra ocular pressure (IOP). Visual acuity and functional integration was evaluated by behavioural experiments and immunohistochemistry, respectively. GFP-expressing ES-NPs transplanted in NMDA-injected RGC-depleted mice differentiated into RGC lineage and possibly integrating into GCL. An improvement in visual acuity was observed after two months of transplantation, when compared to the pre-transplantation values. Expression of c-Fos in the transplanted cells, upon light induction, further suggests functional integration into the host retinal circuitry. However, the transplanted cells did not send axonal projections into optic nerve. Transplantation experiments in DBA/2J mouse showed no significant improvement in visual functions, possibly due to both host and transplanted retinal cell death which could be due to an inherent high IOP. We showed that, transplantation of ES-NPs into the retina of RGC-ablated mouse models could survive, differentiate to RGC lineage, and possibly integrate into GCL to improve visual function. However, for the survival of transplanted cells in glaucoma, strategies to control the IOP are warranted.

Author(s):  
Mundackal S. Divya ◽  
Vazhanthodi A. Rasheed ◽  
Tiffany Schmidt ◽  
Soundararajan Lalitha ◽  
Samer Hattar ◽  
...  

1998 ◽  
Vol 236 (12) ◽  
pp. 904-915 ◽  
Author(s):  
M.-M. Gellrich ◽  
Stephan Neumaier ◽  
Claudia Auw-Hädrich ◽  
Nils-Claudius Gellrich ◽  
Lutz Lothar Hansen

2021 ◽  
Vol 62 (1) ◽  
pp. 5
Author(s):  
Kwame Antwi-Boasiako ◽  
Louvenia Carter-Dawson ◽  
Ronald Harwerth ◽  
Margaret Gondo ◽  
Nimesh Patel

2018 ◽  
Vol 26 (01) ◽  
Author(s):  
Muhammad Shaheer ◽  
Arooj Amjad ◽  
Asima Rafique

ABSTRACT: PURPOSE: To study the changes in Ganglion Cell Complex as measured on OCT after phacoemulsification with intra ocular lens implantation. STUDY DESIGN: Quasi experimental study PLACE AND DURATION OF STUDY: Department of Ophthalmology, Lahore General Hospital, Lahore from 1-3-2017 to 30-4-2018 MATERIALS AND METHODS: Ethical approval of the study was obtained from ‘’Ethical Review Committee’’ of Lahore General Hospital, Lahore. Patients presenting to the Eye OPD Lahore General Hospital were assessed for inclusion and exclusion criteria. All patients (n=64) diagnosed with cataract requiring surgery were included in study. Patients having any coexisting ocular pathology hindering the OCT measurement i.e. Corneal opacity, Vitreous hemorrhage, Retinal detachment were excluded from study. Retinal Ganglion Cell Complex thickness was measured in Superior, Inferior, Supero-Nasal, Supero-Temporal, Infero-Nasal and Infero-Temporal quadrants. Besides that Signal Strength on OCT was also documented. Pre-Operatively, Visual acuity was measured and OCT performed and the findings were recorded on a designed proforma. Post-Operatively, the patients were called for follow-up after one month at which time Visual acuity was again measured and OCT performed and findings recorded in the proforma. All the surgeries were performed by single surgeon. RESULTS: The thickness of Ganglion Cell Complex increased significantly (p<0.001) one month after cataract surgery. CONCLUSION: Cataract surgery does affect the measurement of Retinal Ganglion Cell Complex thickness on OCT.


Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 952
Author(s):  
Genea Edwards ◽  
Yonghoon Lee ◽  
Martha Kim ◽  
Soham Bhanvadia ◽  
Keun-Young Kim ◽  
...  

Oxidative stress is one of major causal factors in glaucomatous neurodegeneration. Ubiquinol promotes retinal ganglion cell (RGC) survival against glaucomatous insults such as oxidative stress. Here we investigated the effect of ubiquinol on RGC survival and/or visual function in mouse models of glaucoma and oxidative stress. DBA/2J and age-matched DBA/2J-Gpnmb+ (D2-Gpnmb+), which do not develop intraocular pressure elevation, or C57BL/6J mice were fed with ubiquinol (1%) or control diet daily for 5 or 2 months. We assessed RGC survival by Brn3a immunohistochemistry and measured expression levels of active and total BAX, peroxisome proliferator-activated receptor-gamma coactivator 1α, transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex protein. Following induction of oxidative stress by paraquat injection, we also assessed visual function. In glaucomatous retina, ubiquinol supplementation significantly promoted RGC survival, blocked BAX activation and increased TFAM and OXPHOS complex II protein expression. Also, ubiquinol supplementation ameliorated oxidative stress-induced visual dysfunction. These findings indicate that ubiquinol promotes RGC survival by increasing TFAM expression and OXPHOS complex II activity in glaucomatous neurodegeneration, and that ubiquinol enhances RGC survival and preserves visual function against oxidative stress. We propose that ubiquinol has a therapeutic potential for treating oxidative stress-associated glaucomatous neurodegeneration.


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