Phototoxic-induced photoreceptor degeneration causes retinal ganglion cell degeneration in pigmented rats

Abstract

Human retinitis pigmentosa results eventually in retinal ganglion cell (RGC) death, but how this occurs remains obscure. We have previously documented that in pigmented dystrophic Royal College of Surgeons (RCS) rats, photoreceptor degeneration is followed by retinal pigment epithelial (RPE) migration, formation of RPE-vascular complexes, and vascular displacement that causes RGC axonal compression and death. To investigate if phototoxic-induced photoreceptor degeneration is capable of causing similar pathologic events, we dilated the left pupil of pigmented nondystrophic RCS and Lister-Hooded rats and exposed them to light (3000 lux) for 72 hours. After various survival periods ranging between 0 hours and 21 months, the retinas were processed as whole mounts or in cross-sections. Two separate retinal degenerative events that may relate to differential light exposure across the retina were observed: an early arciform area of degeneration in the superotemporal retina and a delayed degeneration in the central and ventral retina. Although degeneration in the arciform area was always more severe and developed earlier (sensitive region), both of them showed quite comparable pathologic events to those described for dystrophic RCS rats. RGC axonal compression was seen as soon as 21 days after light exposure and RGC loss was seen 9 months after light exposure, mainly in the superotemporal retina, but also in the ventral retina. The results show that RGC loss in induced photoreceptor degeneration results from a similar series of events to those occurring as a consequence of inherited degeneration and therefore is not uniquely a property of inherited photoreceptor degeneration.

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

“…At late times post-lesion axonal degenerative events similar to those described by Ramón y Cajal are www.intechopen.com observed, such as rosary-like intra-axonal accumulations and club-like axonal ends ( Figure 1D, arrows and arrowhead). The aberrant expression of pNFH in the ganglion cell layer is common to other insults that affect the RGC either primarily, like optic nerve transection or IOP increase , 2010Parrilla-Reverter et al, 2009a;Nguyen et al, 2011), or secondarily, like phototoxicity (Villegas-Pérez et al, 1996Marco-Gomariz et al, 2006;Garcia-Ayuso et al, 2010). It is worth noting than even though all these insults cause the same aberrant patterns, their quantity and time course differs.…”

Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration

“…[50][51][52] Light is a risk factor for some retinal degenerations, [53][54][55][56] and it accelerates photoreceptor degeneration in some inherited retinal degenerations. 54,[57][58][59] In previous work, [18][19][20]50 we documented that light exposure causes rapid photoreceptor degeneration and, longterm, alterations in all the retinal layers and RGC loss. [18][19][20] Here, we show, for the first time, that light exposure causes loss of both S-and L/M-cones, but that the loss of S-cones is greater, suggesting that S-cones are more sensitive to light damage than L/M-cones, in accordance with previously published data.…”

“…54,[57][58][59] In previous work, [18][19][20]50 we documented that light exposure causes rapid photoreceptor degeneration and, longterm, alterations in all the retinal layers and RGC loss. [18][19][20] Here, we show, for the first time, that light exposure causes loss of both S-and L/M-cones, but that the loss of S-cones is greater, suggesting that S-cones are more sensitive to light damage than L/M-cones, in accordance with previously published data. 42,60 We also show that light exposure causes a disruption of the photoreceptor mosaic, characterized by the appearance of rings devoid of cones in the superior retina, similar to those previously observed in some inherited retinal degenerations (see below).…”

“…6 In addition to cone loss, control light-exposed animals also showed a disruption of the normal photoreceptor mosaic: ''empty rings'' devoid of both types of cones (Fig. 6) appeared mainly in the superotemporal retina, in an area coincident with the ''arciform photosensitive area'' previously described by our group [18][19][20] (Fig. 6A), which is the area most affected by light exposure.…”

“…In this work, we have used b-alanine treatment and our model of light-induced retinal damage, [18][19][20] to study the effects of an acute light exposure on the retina of taurine-depleted animals. We have investigated the survival of different retinal neurons ALE using techniques recently developed in our laboratory to identify and map in the same retinal flatmounts the entire population of L/M-and S-cones, Brn3a þ RGCs, and m þ RGCs ALE.…”