Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular Hypertension

Manuel Vidal-Sanz,Giuseppe Rovere,Francisco J Valiente-Soriano,Manuel Salinas-Navarro,Fernando Lucas-Ruiz,Marcelino Aviles-Trigueros,María P Villegas-Pérez,Maria C Sanchez-Migallon,Marta Agudo-Barriuso,Caridad Galindo-Romero,Arturo Ortin-Martinez,Paloma Sobrado-Calvo,Francisco M Nadal-Nicolás

doi:10.3389/fnins.2017.00235

Manuel Vidal-Sanz, Giuseppe Rovere + Show 11 more

Open Access

https://doi.org/10.3389/fnins.2017.00235

Copy DOI

Abstract

Glaucoma, one of the leading causes of blindness worldwide, affects primarily retinal ganglion cells (RGCs) and their axons. The pathophysiology of glaucoma is not fully understood, but it is currently believed that damage to RGC axons at the optic nerve head plays a major role. Rodent models to study glaucoma include those that mimic either ocular hypertension or optic nerve injury. Here we review the anatomical loss of the general population of RGCs (that express Brn3a; Brn3a+RGCs) and of the intrinsically photosensitive RGCs (that express melanopsin; m+RGCs) after chronic (LP-OHT) or acute (A-OHT) ocular hypertension and after complete intraorbital optic nerve transection (ONT) or crush (ONC). Our studies show that all of these insults trigger RGC death. Compared to Brn3a+RGCs, m+RGCs are more resilient to ONT, ONC, and A-OHT but not to LP-OHT. There are differences in the course of RGC loss both between these RGC types and among injuries. An important difference between the damage caused by ocular hypertension or optic nerve injury appears in the outer retina. Both axotomy and LP-OHT induce selective loss of RGCs but LP-OHT also induces a protracted loss of cone photoreceptors. This review outlines our current understanding of the anatomical changes occurring in rodent models of glaucoma and discusses the advantages of each one and their translational value.

Highlights

The mammalian retina is an extension of the central nervous system (CNS) specialized to capture environmental luminous information
We found that the loss of Brn3a+retinal ganglion cells (RGCs) adjusts well to either a segmental linear or to a linear regression (Figure 1B), providing a mathematical model to compare more the damage caused by each lesion in each species and strain
The minute proportion of surviving Brn3a+RGCs contrasts with the much greater proportion of melanopsin expressing RGCs (m+RGCs) that survives by 6 months after optic nerve crush (ONC) or optic nerve transection (ONT)

Summary

Introduction

The mammalian retina is an extension of the central nervous system (CNS) specialized to capture environmental luminous information. Neither insult causes the loss of non-RGC neurons in the ganglion cell layer (Ortín-Martínez et al, 2015; Nadal-Nicolás et al, 2015a) but ocular hypertension results in a secondary damage that reaches the outer retina (Ortín-Martínez et al, 2015).

Results

Conclusion