Abstract
Abstract: :
Background: T cells directed against self–antigens facilitate survival and repair following central nervous system (CNS) injury. Such a protective mechanism is amenable for boosting by active immunization with weak agonists of self–antigens. Here we examined whether a similar neuroprotective effect can be evoked by vaccination with a random copolymer of two amino acids, consisting of only glutamic acid and tyrosine. Methods: Intraocular pressure (IOP) in the rat was unilaterally elevated by lasering of ocular blood vessels (chronic model) or by saline infusion into the anterior chamber (acute model). IOP was measured with Tono–Pen (XL, Mentor®). After IOP elevation, poly–YE or PBS only was administered according to different regimens. IOP–generated damage was assessed after 1 or 2 weeks in the acute model, and after 3 weeks in the chronic model, by retrograde labeling of viable retinal ganglion cells (RGCs) with rhodamine dextran. Vaccinated and control rats were also subjected to immunohistochemical staining for detection of T cells (alpha beta TCR) at several time points after acute elevation of IOP. Results: In the acute glaucoma model, poly–YE vaccination evoked an early, well–controlled increase in local T cell accumulation, which subsided by day 7, and resulted in survival of significantly more RGCs than in control rats (77±6% compared to 46±11%, P<0.05). Vaccination was effective only when given within 24 h of IOP elevation. Similar extents of survival were observed in the chronic IOP model (72.6±4.37% compared to 51.48±1.68%) and with other routes of administration (e.g. eyedrops). Conclusions: Vaccination with Poly–YE was neuroprotective in two glaucoma models. Poly–YE is effective apparently through regulation of local microglia.
Keywords: autoimmune disease • inflammation • intraocular pressure