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

• Published in: Frontiers in neuroscience Vol. 11; p. 235
• Main Authors: Vidal-Sanz, Manuel, Galindo-Romero, Caridad, Valiente-Soriano, Francisco J, Nadal-Nicolás, Francisco M, Ortin-Martinez, Arturo, Rovere, Giuseppe, Salinas-Navarro, Manuel, Lucas-Ruiz, Fernando, Sanchez-Migallon, Maria C, Sobrado-Calvo, Paloma, Aviles-Trigueros, Marcelino, Villegas-Pérez, María P, Agudo-Barriuso, Marta
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 26.04.2017; Frontiers Media S.A
• Subjects: acute ocular hypertension; Animal models; Axons; Axotomy; Blindness; Brn-3 protein; Brn3a retinal ganglion cells; chronic ocular hypertension; Glaucoma; Hypertension; Light; Melanopsin; melanopsin retinal ganglion cells; Neuroscience; Optic nerve; Photoreceptors; Population; Retina; Retinal ganglion cells; Rodents; cone photoreceptors; acute ocular hypertension; glaucoma; chronic ocular hypertension; axotomy; Brn3a retinal ganglion cells; retinal nerve fiber layer; melanopsin retinal ganglion cells
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2017.00235

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.