Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes.

Yuliya Markitantova,Vladimir Simirskii

doi:10.3390/ijms21051602

Abstract

Retinal development is under the coordinated control of overlapping networks of signaling pathways and transcription factors. The paper was conceived as a review of the data and ideas that have been formed to date on homeobox genes mutations that lead to the disruption of eye organogenesis and result in inherited eye/retinal diseases. Many of these diseases are part of the same clinical spectrum and have high genetic heterogeneity with already identified associated genes. We summarize the known key regulators of eye development, with a focus on the homeobox genes associated with monogenic eye diseases showing retinal manifestations. Recent advances in the field of genetics and high-throughput next-generation sequencing technologies, including single-cell transcriptome analysis have allowed for deepening of knowledge of the genetic basis of inherited retinal diseases (IRDs), as well as improve their diagnostics. We highlight some promising avenues of research involving molecular-genetic and cell-technology approaches that can be effective for IRDs therapy. The most promising neuroprotective strategies are aimed at mobilizing the endogenous cellular reserve of the retina.

Highlights

The development of the human eye is controlled by a morphogenetic process that requires precise spatial and temporal gene regulation [1,2]
We focused on inherited retinal diseases (IRDs) associated with single homeobox gene malfunctions as a result of mutations
It is obvious that an integrated approach should keep in mind the multigenic and systemic nature of a number of retinal/eye diseases to chart the way for appropriate personalized genes and cells tIhnte. rJ.aMpoil.eSscit.e20c2h0,n2o1,lxoFgOieRsPEaEnRdREpVhIEaWrmacologic neuroprotection [9,10,11]

Summary

Introduction

The development of the human eye is controlled by a morphogenetic process that requires precise spatial and temporal gene regulation [1,2]. This review highlights the role of the main homeobox genes associated with inherited eye diseases showing retinal manifestations Mutations of these genes leading to vision loss in humans have been identified by genetic screenings. Homeobox genes from different classes include retina-specific regulatory genes accepted as critical for eye field specification and retinal cells type differentiation by a broad array of loss- or gain-of-function models. Among these genes are some that are known to cause inherited retinal diseases (IRDs) that disturb the development, function, and survival of rod and cone photoreceptors, ganglion cells, or retinal pigment epithelial cells [4,6,7,8]. Macroglia, and microglia, as well as the wall cells of the microvessels (endotheliocytes and pericytes) interact with each other and form a blood–retinal barrier that regulates the supply of oxygen and trophic factors to retinal neurons and is involved in recycling of metabolic products [26,27,28]

Homeobox Transcription Factors Expressed in Retina

Findings

Alx Gene Family