Retina

Retina Publications

Uemura A, Fruttiger M, D'Amore PA, De Falco S, Joussen AM, Sennlaub F, Brunck LR, Johnson KT, Lambrou GN, Rittenhouse KD, Langmann T. VEGFR1 signaling in retinal angiogenesis and microinflammation. Prog Retin Eye Res 2021;84:100954.Abstract
Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, -C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Müller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.
Laíns I, Wang JC, Cui Y, Katz R, Vingopoulos F, Staurenghi G, Vavvas DG, Miller JW, Miller JB. Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Prog Retin Eye Res 2021;84:100951.Abstract
The advent of optical coherence tomography (OCT) revolutionized both clinical assessment and research of vitreoretinal conditions. Since then, extraordinary advances have been made in this imaging technology, including the relatively recent development of swept-source OCT (SS-OCT). SS-OCT enables a fast scan rate and utilizes a tunable swept laser, thus enabling the incorporation of longer wavelengths than conventional spectral-domain devices. These features enable imaging of larger areas with reduced motion artifact, and a better visualization of the choroidal vasculature, respectively. Building on the principles of OCT, swept-source OCT has also been applied to OCT angiography (SS-OCTA), thus enabling a non-invasive in depth-resolved imaging of the retinal and choroidal microvasculature. Despite their advantages, the widespread use of SS-OCT and SS-OCTA remains relatively limited. In this review, we summarize the technical details, advantages and limitations of SS-OCT and SS-OCTA, with a particular emphasis on their relevance for the study of retinal conditions. Additionally, we comprehensively review relevant studies performed to date to the study of retinal health and disease, and highlight current gaps in knowledge and opportunities to take advantage of swept source technology to improve our current understanding of many medical and surgical chorioretinal conditions. We anticipate that SS-OCT and SS-OCTA will continue to evolve rapidly, contributing to a paradigm shift to more widespread adoption of new imaging technology to clinical practice.
Townes-Anderson E, Halasz E, Wang W, Zarbin M. Coming of Age for the Photoreceptor Synapse. Invest Ophthalmol Vis Sci 2021;62(12):24.Abstract
Purpose: To discuss the potential contribution of rod and cone synapses to the loss of visual function in retinal injury and disease. Methods: The published literature and the authors' own work were reviewed. Results: Retinal detachment is used as a case study of rod spherule and cone pedicle plasticity after injury. Both rod and cone photoreceptors terminals are damaged after detachment although the structural changes observed are only partially overlapping. For second-order neurons, only those associated with rod spherules respond consistently to injury by remodeling. Examination of signaling pathways involved in plasticity of conventional synapses and in neural development has been and may continue to be productive in discovering novel therapeutic targets. Rho kinase (ROCK) inhibition is an example of therapy that may reduce synaptic damage by preserving normal synaptic structure of rod and cone cells. Conclusions: We hypothesize that synaptic damage contributes to poor visual restoration after otherwise successful anatomical repair of retinal detachment. A similar situation may exist for patients with degenerative retinal disease. Thus, synaptic structure and function should be routinely studied, as this information may disclose therapeutic strategies to mitigate visual loss.
Patel NA, Yannuzzi NA, Lin J, Smiddy WE. A Cost Effectiveness Analysis of Intravitreal Aflibercept for the Prevention of Progressive Diabetic Retinopathy. Ophthalmol Retina 2021;Abstract
PURPOSE: To calculate costs required to prevent center-involved diabetic macular edema (CI-DME) or proliferative diabetic retinopathy (PDR), and to improve the diabetic retinopathy severity score (DRSS) with intravitreal anti-VEGF injections as reported for aflibercept in two randomized control trials. DESIGN: Cost-effectiveness analysis modeling based on published data SUBJECTS: None METHODS: Results from PANORAMA and the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol W were analyzed. Parameters collected included DRSS score, risk reduction of PDR, risk reduction of CI-DME, and number of treatments required. Costs were modeled based on 2020 Medicare reimbursement data practice settings of hospital-based facility and non-facility. MAIN OUTCOME MEASURE: Cost to prevent case of PDR and CI-DME, and to improve DRSS stage RESULTS: Over 2 years in Protocol W, the cost required to prevent 1 case of PDR was $83,000 ($72,400) in the facility (non-facility) setting; in PANORAMA, the corresponding 2 year costs were $89,400 ($75,000) for the 2Q16 arm, and $91,200 ($89,900) for the 2Q8PRN arm. To prevent 1 case of CI-DME with vision loss in Protocol W, the cost was $154,000 ($133,000). For all CI-DME, with and without vision loss; in PANORAMA, the costs to prevent a case were $70,900 ($59,500) for the 2Q16 arm, and $90,000 ($88,800) for the 2Q8PRN arm. In Protocol W, the overall accumulated total for cost /DRSS unit change at the 2 year point for facility (non-facility) setting was $2700 ($2400)/DRSS. In the first year alone, it was $2100 ($1800)/DRSS and in the second year alone, $6100 ($5300)/DRSS. CONCLUSION: There is a considerable cost associated with the prevention of PDR and CI-DME with intravitreal aflibercept injections. A price per unit of change in diabetic retinopathy severity score is a new parameter which might serve as a benchmark in future utility analyses that could be used to bring perspective to cost-utility considerations.
Bannai D, Adhan I, Katz R, Kim LA, Keshavan M, Miller JB, Lizano P. Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography. Schizophr Bull 2021;Abstract
BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.
Maidana DE, Gonzalez-Buendia L, Miller JW, Vavvas DG. Local photoreceptor cell death differences in the murine model of retinal detachment. Sci Rep 2021;11(1):18798.Abstract
To investigate local cell death differences in the attached and detached retina at different regions in a murine experimental retinal detachment model. Subretinal injection of sodium hyaluronate was performed in eight-week-old C57BL/6J mice. Retinal regions of interest were defined in relation to their distance from the peak of the retinal detachment, as follows: (1) attached central; (2) attached paracentral; (3) detached apex; and (4) detached base. At day 0, the outer nuclear layer cell count for the attached central, attached paracentral, detached apex, and detached base was 1247.60 ± 64.62, 1157.80 ± 163.33, 1264.00 ± 150.7, and 1013.80 ± 67.16 cells, respectively. There were significant differences between the detached base vs. attached central, and between detached base vs. detached apex at day 0. The detached apex region displayed a significant and progressive cell count reduction from day 0 to 14. In contrast, the detached base region did not show progressive retinal degeneration in this model. Moreover, only the detached apex region had a significant and progressive cell death rate compared to baseline. Immediate confounding changes with dramatic differences in cell death rates are present across regions of the detached retina. We speculate that mechanical and regional differences in the bullous detached retina can modify the rate of cell death in this model.
Musayeva A, Unkrig JC, Zhutdieva MB, Manicam C, Ruan Y, Laspas P, Chronopoulos P, Göbel ML, Pfeiffer N, Brochhausen C, Daiber A, Oelze M, Li H, Xia N, Gericke A. Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina. Cells 2021;10(9)Abstract
Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in the ganglion cell layer (GCL) of the retina and axons in the optic nerve. Retinal arteriole responses were measured in isolated retinas by video microscopy. The levels of reactive oxygen species (ROS) were assessed in retinal cryosections and redox gene expression was determined in isolated retinas by quantitative PCR. I/R markedly reduced cell number in the GCL and axon number in the optic nerve of the vehicle-treated mice. In contrast, only a negligible reduction in cell and axon number was observed following I/R in the betulinic acid-treated mice. Endothelial function was markedly reduced and ROS levels were increased in retinal arterioles of vehicle-exposed eyes following I/R, whereas betulinic acid partially prevented vascular endothelial dysfunction and ROS formation. Moreover, betulinic acid boosted mRNA expression for the antioxidant enzymes SOD3 and HO-1 following I/R. Our data provide evidence that betulinic acid protects from I/R injury in the mouse retina. Improvement of vascular endothelial function and the reduction in ROS levels appear to contribute to the neuroprotective effect.
Peterson SL, Li Y, Sun CJ, Wong KA, Leung KS, de Lima S, Hanovice NJ, Yuki K, Stevens B, Benowitz LI. Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve. J Neurosci 2021;Abstract
Axon regenerative failure in the mature CNS contributes to functional deficits following many traumatic injuries, ischemic injuries and neurodegenerative diseases. The complement cascade of the innate immune system responds to pathogen threat through inflammatory cell activation, pathogen opsonization, and pathogen lysis, and complement is also involved in CNS development, neuroplasticity, injury, and disease. Here, we investigated the involvement of the classical complement cascade and microglia/monocytes in CNS repair using the mouse optic nerve injury (ONI) model, in which axons arising from retinal ganglion cells (RGCs) are disrupted. We report that central complement C3 protein and mRNA, classical complement C1q protein and mRNA, and microglia/monocyte phagocytic complement receptor CR3 all increase in response to ONI, especially within the optic nerve itself. Importantly, genetic deletion of C1q, C3, or CR3 attenuates RGC axon regeneration induced by several distinct methods, with minimal effects on RGC survival. Local injections of C1q function-blocking antibody revealed that complement acts primarily within the optic nerve, not retina, to support regeneration. Moreover, C1q opsonizes and CR3+ microglia/monocytes phagocytose growth-inhibitory myelin debris after optic nerve injury, a likely mechanism through which complement and myeloid cells support axon regeneration. Collectively, these results indicate that local optic nerve complement-myeloid phagocytic signaling is required for CNS axon regrowth, emphasizing the axonal compartment and highlighting a beneficial neuro-immune role for complement and microglia/monocytes in CNS repair.SIGNIFICANCE STATEMENTDespite the importance of achieving axon regeneration after CNS injury and the inevitability of inflammation after such injury, the contributions of complement and microglia to CNS axon regeneration are largely unknown. Whereas inflammation is commonly thought to exacerbate the effects of CNS injury, we find that complement proteins C1q and C3 and microglia/monocyte phagocytic complement receptor CR3 are each required for retinal ganglion cell axon regeneration through the injured mouse optic nerve. Also, whereas studies of optic nerve regeneration generally focus on the retina, we show that the regeneration-relevant role of complement and microglia/monocytes likely involves myelin phagocytosis within the optic nerve. Thus, our results point to the importance of the innate immune response for CNS repair.
Konstantinou EK, Shaikh N, Ramsey DJ. Birt-Hogg-Dubé syndrome associated with chorioretinopathy and nyctalopia: a case report and review of the literature. Ophthalmic Genet 2021;:1-7.Abstract
PURPOSE: To report a rare case of Birt-Hogg-Dubé Syndrome (BHD) with progressive chorioretinopathy. METHODS: Case report. RESULTS: A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy. CONCLUSION: BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities. ABBREVIATIONS: BHD: Birt-Hogg-Dubé syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive.
Avraham D, Jung J-H, Yitzhaky Y, Peli E. Retinal prosthetic vision simulation: temporal aspects. J Neural Eng 2021;18(4)Abstract
Objective. The perception of individuals fitted with retinal prostheses is not fully understood, although several retinal implants have been tested and commercialized. Realistic simulations of perception with retinal implants would be useful for future development and evaluation of such systems.Approach.We implemented a retinal prosthetic vision simulation, including temporal features, which have not been previously simulated. In particular, the simulation included temporal aspects such as persistence and perceptual fading of phosphenes and the electrode activation rate.Main results.The simulated phosphene persistence showed an effective reduction in flickering at low electrode activation rates. Although persistence has a positive effect on static scenes, it smears dynamic scenes. Perceptual fading following continuous stimulation affects prosthetic vision of both static and dynamic scenes by making them disappear completely or partially. However, we showed that perceptual fading of a static stimulus might be countered by head-scanning motions, which together with the persistence revealed the contours of the faded object. We also showed that changing the image polarity may improve simulated prosthetic vision in the presence of persistence and perceptual fading.Significance.Temporal aspects have important roles in prosthetic vision, as illustrated by the simulations. Considering these aspects may improve the future design, the training with, and evaluation of retinal prostheses.
Huang X, Sun J, Majoor J, Vermeer KA, Lemij H, Elze T, Wang M, Boland MV, Pasquale LR, Mohammadzadeh V, Nouri-Mahdavi K, Johnson C, Yousefi S. Estimating the Severity of Visual Field Damage From Retinal Nerve Fiber Layer Thickness Measurements With Artificial Intelligence. Transl Vis Sci Technol 2021;10(9):16.Abstract
Purpose: The purpose of this study was to assess the accuracy of artificial neural networks (ANN) in estimating the severity of mean deviation (MD) from peripapillary retinal nerve fiber layer (RNFL) thickness measurements derived from optical coherence tomography (OCT). Methods: Models were trained using 1796 pairs of visual field and OCT measurements from 1796 eyes to estimate visual field MD from RNFL data. Multivariable linear regression, random forest regressor, support vector regressor, and 1D convolutional neural network (CNN) models with sectoral RNFL thickness measurements were examined. Three independent subsets consisting of 698, 256, and 691 pairs of visual field and OCT measurements were used to validate the models. Estimation errors were visualized to assess model performance subjectively. Mean absolute error (MAE), root mean square error (RMSE), median absolute error, Pearson correlation, and R-squared metrics were used to assess model performance objectively. Results: The MAE and RMSE of the ANN model based on the testing dataset were 4.0 dB (95% confidence interval = 3.8-4.2) and 5.2 dB (95% confidence interval = 5.1-5.4), respectively. The ranges of MAE and RMSE of the ANN model on independent datasets were 3.3-5.9 dB and 4.4-8.4 dB, respectively. Conclusions: The proposed ANN model estimated MD from RNFL measurements better than multivariable linear regression model, random forest, support vector regressor, and 1-D CNN models. The model was generalizable to independent data from different centers and varying races. Translational Relevance: Successful development of ANN models may assist clinicians in assessing visual function in glaucoma based on objective OCT measures with less dependence on subjective visual field tests.
Han H, Yang Y, Liu B, Tian J, Dong L, Qi H, Zhu W, Wang J, Lei H. Chalcomoracin prevents vitreous-induced activation of AKT and migration of retinal pigment epithelial cells. J Cell Mol Med 2021;Abstract
Retinal pigment epithelial (RPE) cells are the major cell type in the epi- or sub-retinal membranes in the pathogenesis of proliferative vitreoretinopathy (PVR), which is a blinding fibrotic eye disease and still short of effective medicine. The purpose of this study is to demonstrate whether Chalocomoracin (CMR), a novel purified compound from fungus-infected mulberry leaves, is able to inhibit vitreous-induced signalling events and cellular responses intrinsic to PVR. Our studies have revealed that the CMR IC50 for ARPE-19 cells is 35.5 μmol/L at 72 hours, and that 5 μmol/L CMR inhibits vitreous-induced Akt activation and p53 suppression; in addition, we have discovered that this chemical effectively blocks vitreous-stimulated proliferation, migration and contraction of ARPE-19 cells, suggesting that CMR is a promising PVR prophylactic.
Zhu R-L, Fang Y, Yu H-H, Chen DF, Yang L, Cho K-S. Absence of ephrin-A2/A3 increases retinal regenerative potential for Müller cells in Rhodopsin knockout mice. Neural Regen Res 2021;16(7):1317-1322.Abstract
Müller cells (MC) are considered dormant retinal progenitor cells in mammals. Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain. It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC. Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller cells. In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC. The level of ephrinAs/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC. Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2-/- A3-/- mice by 5-ethynyl-2'-deoxyuridine (EdU) incorporation. We detected a significant increase of EdU+ cells in MC derived from A2-/- A3-/- mice. Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout (Rho-/-) mice. To further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2-/- A3-/- , Rho-/- and Rho-/- A2-/- A3-/- mice and the numbers of EdU+ cells distributed among different layers of the retina. EphrinAs/EphA4 expression was upregulated in the retina of Rho-/- mice compared to the wild-type mice. In addition, cultured MC derived from ephrin-A2-/- A3-/- mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type mice. Interestingly, we detected a significant increase of EdU+ cells in the retinas of adult ephrin-A2-/- A3-/- mice mainly in the inner nuclear layer; and these EdU+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from MC. In Rhodopsin knockout mice (Rho-/- A2-/- A3-/- mice), a significantly greater amount of EdU+ cells were located in the ciliary body, retina and RPE than that of Rho-/- mice. Comparing between 6 and 12 weeks old Rho-/- A2-/- A3-/- mice, we recorded more EdU+ cells in the outer nuclear layer in the 12-week-old mice undergoing severe retinal degeneration. Taken together, Ephrin-A2/A3 are negative regulators of the proliferative and neurogenic potentials of MC. Absence of ephrin-A2/A3 promotes the migration of proliferating cells into the outer nuclear layer and may lead to retinal cell regeneration. All experimental procedures were approved by the Animal Care and Use Committee at Schepens Eye Research Institute, USA (approval No. S-353-0715) on October 24, 2012.
Nigalye A, Pundlik S, Kim J, Luo G, Husain D. Delayed dark adaptation in central serous chorioretinopathy. Am J Ophthalmol Case Rep 2021;22:101098.Abstract
Purpose: To evaluate the effect of central serous chorioretinopathy (CSCR) on retinal function using dark adaptation in a human subject, and to follow it through resolution of the disease. Patients: Single patient, 50 years old male patient, with acute CSCR in one eye and resolved old CSCR in the other eye. Observations: Observational study in patient with CSCR followed through resolution of the subretinal fluid (52 days). Dark adaptation was assessed using the AdaptDx® (Maculogix Inc.) measured by Rod Intercept time (RIT) in minutes. A normal retinal locus of the same eye on the opposite side of the fovea was used as control. Retinal separation (microns) was measured using Spectralis Optical Coherence Tomography (Spectralis®, HRA + OCT, Heidelberg engineering). Change in time to dark adapt, were correlated with retinal separation measured in microns, during the course of CSCR.The Rod Intercept time was delayed in the area of detached retina compared to the normal region (control) on presentation with retinal separation (RS) of 104 μm. The Rod Intercept time returned to normal as the retinal separation from retinal pigment epithelium decreased and eventually resolved. Conclusions: This case shows that delay in dark adaptation is proportional to the amount of separation of neurosensory retina from retinal pigment epithelium in CSCR, this may offer a potential of using DA to characterize visual function in CSCR. The association of dark adaptation response with the state of retinal pigment epithelial function and its ability to predict the recurrence of CSCR needs further evaluation.
Oswald J, Kegeles E, Minelli T, Volchkov P, Baranov P. Transplantation of miPSC/mESC-derived retinal ganglion cells into healthy and glaucomatous retinas. Mol Ther Methods Clin Dev 2021;21:180-198.Abstract
Optic neuropathies, including glaucoma, are a group of neurodegenerative diseases, characterized by the progressive loss of retinal ganglion cells (RGCs), leading to irreversible vision loss. While previous studies demonstrated the potential to replace RGCs with primary neurons from developing mouse retinas, their use is limited clinically. We demonstrate successful transplantation of mouse induced pluripotent stem cell (miPSC)/mouse embryonic stem cell (mESC)-derived RGCs into healthy and glaucomatous mouse retinas, at a success rate exceeding 65% and a donor cell survival window of up to 12 months. Transplanted Thy1-GFP+ RGCs were able to polarize within the host retina and formed axonal processes that followed host axons along the retinal surface and entered the optic nerve head. RNA sequencing of donor RGCs re-isolated from host retinas at 24 h and 1 week post-transplantation showed upregulation of cellular pathways mediating axonal outgrowth, extension, and guidance. Additionally, we provide evidence of subtype-specific diversity within miPSC-derived RGCs prior to transplantation.

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