Caspase-7: a critical mediator of optic nerve injury-induced retinal ganglion cell death

Reduction in caspase-7 expression in the retina of Casp7 −/− mice. Representative western blot images of pro-caspase-7 in protein extracts from retinas from WT and Casp7 −/− mice. (TIFF 42 kb

Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model

<p>Abstract</p> <p>Background</p> <p>Nitric oxide synthase 2 (NOS2) contributes to neural death in some settings, but its role in glaucoma remains controversial. NOS2 is implicated in retinal ganglion cell degeneration in a rat glaucoma model in which intraocular pressure (IOP) is experimentally elevated by blood vessel cauterization, but not in a rat glaucoma model where IOP was elevated by injection of hypertonic saline. To test the importance of NOS2 for an inherited glaucoma, in this study we both genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse glaucoma model.</p> <p>Methods</p> <p>The expression of <it>Nos2 </it>in the optic nerve head was analyzed at both the RNA and protein levels at different stages of disease pathogenesis. To test the involvement of <it>Nos2 </it>in glaucomatous neurodegeneration, a null allele of <it>Nos2 </it>was backcrossed into DBA/2J mice and the incidence and severity of glaucoma was assessed in mice of each <it>Nos2 </it>genotype. Additionally, DBA/2J mice were treated with the NOS2 inhibitor aminoguanidine and the disease compared to untreated mice.</p> <p>Results</p> <p>Optic nerve head <it>Nos2 </it>RNA levels varied and increased during moderate but decreased at early and severe stages of disease. Despite the presence of a few NOS2 positive cells in the optic nerve head, NOS2 protein was not substantially increased during the glaucoma. Genetic deficiency of <it>Nos2 </it>or aminoguanidine treatment did not alter the IOP profile of DBA/2J mice. Additionally, neither <it>Nos2 </it>deficiency nor aminoguanidine had any detectable affect on the glaucomatous optic nerve damage.</p> <p>Conclusion</p> <p>Glaucomatous neurodegeneration in DBA/2J mice does not require NOS2 activity. Further experiments involving various models are needed to assess the general importance of <it>Nos2 </it>in glaucoma.</p

Involvement of Nrf2 in Ocular Diseases

The human body harbors within it an intricate and delicate balance between oxidants and antioxidants. Any disruption in this checks-and-balances system can lead to harmful consequences in various organs and tissues, such as the eye. This review focuses on the effects of oxidative stress and the role of a particular antioxidant system—the Keap1-Nrf2-ARE pathway—on ocular diseases, specifically age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma. Together, they are the major causes of blindness in the world