Dataset Information

The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies.

ABSTRACT: Basement membranes help to establish, maintain, and separate their associated tissues. They also provide growth and signaling substrates for nearby resident cells. The internal limiting membrane (ILM) is the basement membrane at the ocular vitreoretinal interface. While the ILM is essential for normal retinal development, it is dispensable in adulthood. Moreover, the ILM may constitute a significant barrier to emerging ocular therapeutics, such as viral gene therapy or stem cell transplantation. Here we take a neurodevelopmental perspective in examining how retinal neurons, glia, and vasculature interact with individual extracellular matrix constituents at the ILM. In addition, we review evidence that the ILM may impede novel ocular therapies and discuss approaches for achieving retinal parenchymal targeting of gene vectors and cell transplants delivered into the vitreous cavity by manipulating interactions with the ILM.

SUBMITTER: Zhang KY

PROVIDER: S-EPMC8087649 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies.

Zhang Kevin Y KY Johnson Thomas V TV

Experimental eye research 20210320

Basement membranes help to establish, maintain, and separate their associated tissues. They also provide growth and signaling substrates for nearby resident cells. The internal limiting membrane (ILM) is the basement membrane at the ocular vitreoretinal interface. While the ILM is essential for normal retinal development, it is dispensable in adulthood. Moreover, the ILM may constitute a significant barrier to emerging ocular therapeutics, such as viral gene therapy or stem cell transplantation. ...[more]

PMID: 33753089

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Project description:BackgroundEpiretinal membranes (ERMs) have been reported after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Peeling of the internal limiting membrane (ILM) can prevent post-PPV ERM formation but has a potential negative impact on macular structure and function.PurposeTo investigate the anatomical and functional outcomes of ILM peeling during PPV for primary RRD.MethodsThis was a prospective nonrandomized study that included 60 eyes of 60 patients with a primary macula-off RRD and less than grade C proliferative vitreoretinopathy (PVR). Eyes were allocated into 2 groups; Group A underwent PPV without ILM peeling and Group B had ILM peeling. At postoperative month 6, all patients underwent retinal imaging using spectral domain optical coherence tomography (OCT) and OCT angiography and macular function was assessed using multifocal electroretinogram (mfERG). Baseline characteristics and postoperative anatomical and visual outcomes were recorded and statistically analyzed.ResultsWe enrolled 30 eyes of 30 patients in each group. In Group A, mean age was 44.6 years, while the mean age of Group B patients was 49.9 years. Postoperative LogMAR visual acuity was significantly better in Group A than in Group B (p < 0.001). ERMs were demonstrated on OCT in 13.3% of Group A and none of Group B patients (p = 0.04). Retinal dimples were found in 53.3% of Group B and none of Group A eyes (p < 0.001). OCTA showed a greater vessel density of the superficial capillary plexus (SCP) in Group A compared to Group B eyes (p = 0.046), while no difference was found regarding deep capillary vessel density (p = 0.7). Mean amplitude of mfERG P1 wave was significantly higher in Group A eyes than in Group B (p = 0.002). Both the SCP vessel density and P1 amplitude were positively correlated with visual acuity (p < 0.001).ConclusionThis study suggests that ILM peeling prevents ERM development in eyes undergoing PPV for uncomplicated macula-off RRD, but potential damage to macular structure and function were found.Trial registration Retrospectively registered on 09/24/2019 on ClinicalTrials.gov with an ID of NCT04139811.

Project description:Proper neural circuit formation requires the precise regulation of neuronal migration, axon guidance, and dendritic arborization. Mutations affecting the function of the transmembrane glycoprotein dystroglycan cause a form of congenital muscular dystrophy that is frequently associated with neurodevelopmental abnormalities. Despite its importance in brain development, the role of dystroglycan in regulating retinal development remains poorly understood. Using a mouse model of dystroglycanopathy (ISPDL79* ) and conditional dystroglycan mutants of both sexes, we show that dystroglycan is critical for the proper migration, axon guidance, and dendritic stratification of neurons in the inner retina. Using genetic approaches, we show that dystroglycan functions in neuroepithelial cells as an extracellular scaffold to maintain the integrity of the retinal inner limiting membrane. Surprisingly, despite the profound disruptions in inner retinal circuit formation, spontaneous retinal activity is preserved. These results highlight the importance of dystroglycan in coordinating multiple aspects of retinal development.SIGNIFICANCE STATEMENT The extracellular environment plays a critical role in coordinating neuronal migration and neurite outgrowth during neural circuit development. The transmembrane glycoprotein dystroglycan functions as a receptor for multiple extracellular matrix proteins and its dysfunction leads to a form of muscular dystrophy frequently associated with neurodevelopmental defects. Our results demonstrate that dystroglycan is required for maintaining the structural integrity of the inner limiting membrane (ILM) in the developing retina. In the absence of functional dystroglycan, ILM degeneration leads to defective migration, axon guidance, and mosaic spacing of neurons and a loss of multiple neuron types during retinal development. These results demonstrate that disorganization of retinal circuit development is a likely contributor to visual dysfunction in patients with dystroglycanopathy.

Dataset Information

The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies.

Publications

The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies.

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