PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration.

Front Cell Neurosci

Medical Research Council, Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.

Published: March 2018

The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb) are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM) and , thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human (CRB1) gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884931PMC
http://dx.doi.org/10.3389/fncel.2018.00090DOI Listing

Publication Analysis

Top Keywords

retinal degeneration
12
photoreceptor morphogenesis
8
morphogenesis retinal
8
fly photoreceptor
8
par complex
8
photoreceptor
5
par-complex crumbs
4
crumbs function
4
function photoreceptor
4
morphogenesis
4

Similar Publications

Mettl3-Mediated m6A Modification is Essential for Visual Function and Retinal Photoreceptor Survival.

Invest Ophthalmol Vis Sci

December 2024

The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Purpose: N6-methyladenosine (m6A) modification, one of the most common epigenetic modifications in eukaryotic mRNA, has been shown to play a role in the development and function of the mammalian nervous system by regulating the biological fate of mRNA. METTL3, the catalytically active component of the m6A methyltransferase complex, has been shown to be essential in development of in the retina. However, its role in the mature retina remains elusive.

View Article and Find Full Text PDF

Purpose: This review explores the role of pigment epithelium-derived factor (PEDF) in retinal degenerative and vascular disorders and assesses its potential both as an adjunct to established vascular endothelial growth factor inhibiting treatments for retinal vascular diseases and as a neuroprotective therapeutic agent.

Methods: A comprehensive literature review was conducted, focusing on the neuroprotective and anti-angiogenic properties of PEDF. The review evaluated its effects on retinal health, its dysregulation in ocular disorders, and its therapeutic application in preclinical models.

View Article and Find Full Text PDF

Glaucoma encompasses a spectrum of disorders characterized by the chronic degeneration of retinal ganglion cell (RGC) axons and the progressive loss of RGCs, resulting in visual impairment. In this study, we investigated the effect of autophagy deficiency on two glaucoma hypertensive models, the DBA/2J spontaneous glaucoma model, and the TGFβ2 (transforming growth factor β2) chronic ocular hypertensive model. For this, we used the and DBA/2J- mice, this latter generated in our laboratory via CRISPR/Cas9 technology, which display impaired autophagy.

View Article and Find Full Text PDF

Background: Age-related macular degeneration (AMD) is a significant factor causing blindness in adults. However, the clinical diagnosis of AMD is relatively challenging, due to the shortcomings of the existing clinical examination methods and the latent period of retinal damage before macular degeneration becomes apparent. This study aims to explore the potential of extracellular vesicles (EVs) protein chips for early diagnosis of AMD using patients' plasma samples.

View Article and Find Full Text PDF

Adeno-associated virus (AAV)-based vectors are the most frequently used platform for retinal gene therapy. Initially explored for the treatment of loss-of-function mutations underpinning many inherited retinal diseases, AAV-based ocular gene therapies are increasingly used to transduce endogenous cells to produce therapeutic proteins, thus producing site-specific biofactories. Relatively invasive ocular routes of administration (ROA) mean prominent procedure-related in-life, and histopathological findings may be observed with some regularity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!