S. Joly

Receptor protein tyrosine phosphatase sigma inhibits axon regrowth in the adult injured CNS

Recently, receptor protein tyrosine phosphatase-sigma (RPTPsigma) has been shown to inhibit axon regeneration in injured peripheral nerves. Unlike the peripheral nervous system (PNS), central nervous system (CNS) neurons fail to regenerate their axons after injury or in disease. In order to assess the role of RPTPsigma in CNS regeneration, we used the retinocollicular system of adult mice lacking RPTPsigma to evaluate retinal ganglion cell (RGC) axon regrowth after optic nerve lesion. Quantitative analysis demonstrated a significant increase in the number of RGC axons that crossed the glial scar and extended distally in optic nerves from RPTPsigma (-/-) mice compared to wild-type littermate controls. Although we found that RPTPsigma is expressed by adult RGCs in wild-type mice, the retinas and optic nerves of adult RPTPsigma (-/-) mice showed no histological defects. Furthermore, the time-course of RGC death after nerve lesion was not different between knockout and wild-type animals. Thus, enhanced axon regrowth in the absence of RPTPsigma could not be attributed to developmental defects or increased neuronal survival. Finally, we show constitutively elevated activity of mitogen-activated protein kinase (MAPK) and Akt kinase in adult RPTPsigma (-/-) mice retinas, suggesting that these signaling pathways may contribute to promoting RGC axon regrowth following traumatic nerve injury. Our results support a model in which RPTPsigma inhibits axon regeneration in the adult injured CNS.

The photopic ERG of the albino guinea pig (Cavia porcellus) : A model of the human photopic ERG

Altricial rodents such as rats and mice are probably the most widely used animal model in the electroretinogram (ERG) literature. However, while the scotopic responses of these rodents share obvious similarities with that of humans, their photopic electroretinograms are strikingly different. For instance, the photopic ERGs of rats and mice include, when measurable, a minimal a-wave, while the b-wave is of much larger amplitude than that of humans. The purpose of this study is to present the albino guinea pig which is like humans, is a precocial animal, and is a better rodent model of the human photopic ERG. In order to investigate the above, photopic electroretinograms and oscillatory potentials, obtained from guinea pigs and human subjects, were compared. Furthermore, in a subset of animals we injected, intravitreally, selective blockers of the ON- (L-2-amino-4-phosphonobutyric acid: L-AP-4; 10xa0mM) or OFF- (kynurenic acid: KYN; 50xa0mM) retinal pathways in order to mimic similar retinal disorders found in human. Based on our results, we believe that, compared to rats and mice, the photopic (cone-mediated) ERG of the guinea pig clearly represents a superior rodent model of the human photopic ERG.

Structural and functional consequences of bright light exposure on the retina of neonatal rats

In a previous study we showed that juvenile rats exposed, for various durations of time, to a bright luminous environment between P14 (eye opening) and P34 developed a light-induced retinopathy (LIR), the severity of which depending on the duration of exposure as well as the age of the rat at the onset of exposure. Our study also revealed that the severity of the LIR increased as the time elapsed between the cessation of exposure and the structural/functional evaluation increased, suggesting that the LIR degenerative process proceeded in two distinct steps namely, an initial (rapid) acute phase that was followed by a (slower) chronic phase. In view of the above, the purpose of the present study was to reinvestigate previous claims suggesting that exposure to bright light prior to eyelid opening had no measurable consequences on the retinal structure and function; the claim being that despite a non-detectable acute phase, bright light exposure prior to eyelid opening could nonetheless yield a significant retinopathy during the chronic phase of development of LIR. In order to test our hypothesis, neonatal rats were raised in a bright luminous environment from birth to P14. At P30, analysis of the results obtained from rats exposed between P0–P14 did not reveal, as previously acknowledged by others, significant LIR damages. However, results obtained at P60 disclosed significant functional anomalies with relative sparing of the retinal ultrastructure. Our results confirm that, in spite of closed eyelids, postnatal exposure to bright environment did trigger a slow degenerative process.