Neuroprotection of retinal ganglion cell function and their central nervous system targets

Abstract

Technological advances have enabled the observation of a large number of retinal ganglion cells (RGCs) in an objective manner. In animal models, it has been shown how retinal ischaemia induces profound functional and structural alterations of the inner retinal and RGC layers by 3 months. These findings reflect degeneration of the inner retinal layers, the RGC population and of the retinotectal projection. Functionally, this implies a permanent disconnection of the retina from its main retinorecipient target region in the brain. Brimonidine, a selective a-2 adrenergic agonist, has been shown to activate a-2 adrenergic receptors in the retina and promote the survival and function of RGCs post-injury. This agent may prevent or diminish ischaemia-induced alterations in the inner and RGC areas as well as in the main retinofugal projection. Understanding the pattern of degeneration that occurs in the major retinofugal pathway following retinal ischaemia will benefit ongoing studies conducted to develop neuroprotectant-based treatment strategies for progressive neuropathies such as glaucoma.

Melanopsin-Containing or Non-Melanopsin–Containing Retinal Ganglion Cells Response to Acute Ocular Hypertension With or Without Brain-Derived Neurotrophic Factor Neuroprotection

“…A transient insult to the retina triggers a protracted degenerative event in the RGC population; for example, 75 minutes of acute elevation of the intraocular pressure induces retinal ischemia and ocular deformation that leads within the first week to the death of approximately 65% of the RGC population, and this is followed by a protracted additional loss of approximately 22% of the RGC population by day 45. Such a time-dependent loss of RGCs is in agreement with previous studies in adult rats in which retrograde labeling 32,[53][54]70 or immunocytochemical 52,55 techniques were employed to identify and count RGCs following transient ischemia of the retina. The effects of AOH on the thickness of the retinal layers were not investigated in the present study, but previous studies following the transient ischemia of the retina induced by selective ligature of the ophthalmic vessels indicate an important decrease in retinal layer thickness with time 71 or even in the overall volume of the superficial layers of the contralateral superior colliculus, which receive the main input from the injured eye.…”

“…30 Retinal injuries may result in RGC loss, which may be prevented with a number of neuroprotective substances. [31][32][33][34][35] Among the RGC neuroprotective agents, the neurotrophin brain derived neurotrophic factor (BDNF) has been shown to be the most efficacious, [36][37][38] but its effects are only transient and thus result in delayed RGC death. [39][40][41][42][43] BDNF has also been shown to be neuroprotective for the general population of RGCs against acute 31,[44][45] or chronic ocular hypertension, 17,[46][47][48][49][50] but not for the population of m þ RGCs.…”

Retinal neurodegeneration in experimental glaucoma

“…In the experimental mice, there was a marked reduction in the amount of CTB-labeled retinal afferents in the superficial layers of the contralateral SC; there were small patches in which CTB labeling was reduced allowing observation of individual axons and their terminal arborizations. In addition, there were areas with little to none CTB immunoreactivity that often presented the form of a column extending in the dorsoventral axis of the visual layers of the SC, resembling the deployment of rodent axon terminals (Ling et al, 1998) and suggesting degeneration of retinal axons and their terminals, as observed following other types of retinal insults (Avilés-Trigueros et al, 2003;MayorTorroglosa et al, 2005;Vidal-Sanz et al, 2007). The lateral extension of these areas varied from a small narrow column to almost one half or more of the SC mediolateral extension (Fig.…”

Regeneración axonal de las células ganglionares de la retina de ratones albinos en injerto autólogo de nervio periférico

“…La cuantificación de las CGRs se ha aplicado en roedores a diferentes modelos experimentales de enfermedades de retina, como: isquemia-reperfusión (Sellés-Navarro et al, 1996;Lam et al, 1997;Lafuente et al, 2001Lafuente et al, , 2002Vidal-Sanz et al, 2007), aplastamiento parcial o total del nervio óptico (Yoles et al, 1999;Parrilla-Reverter et al, 2009a, b;Nadal-Nicolas 2009, axotomía de nervio óptico (Vidal-Sanz et al,.1988, Peinado-Ramón et al,. 1996, Nadal-Nicolas et al, .2009, Galindo-Romero et al, 2011, Sánchez-Migallón, et al, 2011, inyección citotóxica (Vorwerk et al, 1996) o elevación crónica de la presión intraocular (Laquis et al, 1988, Sawada y Nevfeld 1999Salinas-Navarro et al, 2009c.…”

“…Mediante el contaje automático obtenemos el valor exacto de la población total de las CGRs (Danias et al, 2002;Marco-Gomariz et al, 2006;Vidal-sanz et al, 2007;Nadal-Nicolás et al, 2009;Salinas-Navarro et al, 2009a, b;García-Ayuso et al, 2010;Galindo-Romero et al, 2011). El contaje automático es un procedimiento reproducible, rápido y objetivo que permite el análisis de un gran número de retinas, evita la pérdida de información y sesgo en la estimación que se genera por el método de muestreo ya que el área muestreada normalmente es una pequeña porción de la retina (como máximo el 15% del total).…”