Frank Schuettauf

Effects of anti-glaucoma medications on gangion cell survival: the DBA/2J mouse model

We studied whether several agents, approved or undergoing trials in human glaucoma, were effective in preventing ganglion cell loss in the DBA/2J mouse. Adult DBA/2J mice were treated with timolol, pilocarpine, brimonidine, dorzolamide, or NMDA-receptor antagonist memantine. Surviving retinal ganglion cells of treated and control mice were retrogradely labeled with fluorogold and counted after whole mount preparation. In treated mice, only memantine and timolol had significant effects on retinal ganglion cell survival (P<0.0001, analysis of variance). Brimonidine was lethal to these mice, and these retinae were not analyzed further. The DBA/2J mouse represents a promising candidate for further experimentation in ocular hypertension.

Adeno-associated viruses containing bFGF or BDNF are neuroprotective against excitotoxicity

Purpose. Brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) hold much promise for the protection of retinal ganglion cells against excitotoxic cell death. We tested the possibility of delivering these growth factors to retinal ganglion cells via an adeno-associated viral (AAV) vector and tested their efficacy in two models of excitotoxicity. Methods. Rat retinas were infected with AAV vectors encoding bFGF or BDNF. A control vector containing green fluorescent protein (GFP) was injected in the contralateral eye. Eyes were subjected to either an intravitreal injection of N-methyl-D-aspartate (NMDA) or optic nerve crush, and ganglion cell survival was evaluated. Results. AAV.CMV.bFGF and AAV.CBA.BDNF were neuroprotective against NMDA injection 1 month post-treatment. Additionally, AAV.CMV.bFGF was protective against optic nerve crush. Conclusion. AAV-mediated delivery of bFGF and BDNF can promote retinal cell survival following excitotoxic insult.

Neuroprotective effects of cardiotrophin-like cytokine on retinal ganglion cells

BackgroundPremature neuronal cell death is a feature of numerous central nervous system and eye diseases, including glaucoma. Neurons (including retinal ganglion cells, RGCs) are protected by several neurotrophic factors, among those the IL-6 family of cytokines. Lately, a novel member of the IL-6 family of cytokines has been identified and cloned. This cytokine is known as novel neurotrophin-1/B-cell-stimulating factor-3 (NNT-1/BSF-3) or cardiotrophin-like cytokine (CLC). It shows neurotrophic as well as B-cell stimulatory effects.MethodsIn this study, the neuroprotective properties of CLC on RGC loss in vivo were investigated.ResultsCLC significantly protected RGCs from degeneration in both chosen models of retinal neuronal damage: optic nerve crush (P<0.01) and N-methyl-D-aspartate (NMDA) injection (P<0.001).ConclusionsCLC shows neuroprotective effects on RGCs in vivo and might be a treatment option for chronic neurodegenerative eye diseases such as glaucoma. Clinical feasibility for the substance requires further investigation since the immunomodulatory and possible adverse effects have not yet been thoroughly characterized.

Caspase inhibitors protect against NMDA-mediated retinal ganglion cell death

Background:u2002 Apoptosis is a major mechanism of cell death in glutamate‐induced excitotoxicity and caspases as the executors of apoptosis play an important role in the development of various central nervous system and eye diseases. We studied the involvement of certain caspases in excitotoxic retinal ganglion cell death, which was experimentally induced in Brown Norway Rats by application of the glutamate receptor agonist N‐methyl‐D‐aspartate (NMDA).