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Eric F. Thee, Kin-Sang Cho, Martine J. Jager, Dong Feng Chen; Immune tolerance to HSP60 attenuates neurodegeneration in a mouse model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6142.
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© ARVO (1962-2015); The Authors (2016-present)
A link between autoimmune responses to heat shock proteins (HSPs) and the pathogenesis of glaucoma has been suggested, but not been proven. Recently, we showed that elevated intraocular pressure (IOP) induced T cell-mediated autoimmune responses to HSP60. Here we propose to test if induction of tolerance to HSP60 attenuates glaucomatous damage.
Immune tolerance to HSP60 was induced in 6-8 week old male and female C57BL/6J mice by administration of a low dose of HSP60 into the nostrils. Control mice were treated with saline. Glaucoma was induced by two injections of microbeads (MB) into the anterior chamber, maintaining IOP elevation for 8 weeks. IOP was monitored weekly. Visual function was assessed by optokinetic motor response (OMR) and electroretinogram scotopic threshold response (pSTR). Mice were sacrificed at 2, 4 and 8 weeks. Immune responses and T cell tolerance to HSP60 were analyzed by fluorence-activated cell sorting (FACS). Glaucomatous neural damage was quantified by retinal ganglion cell (RGC) and axon counts.
Nostril administration of low dose HSP60 induced immune tolerance and increased levels of Treg as shown by FACS analysis. By 4 weeks, MB-injected eyes displayed an IOP of 20.0±0.56 mmHg or above as compared to 11.6±0.21 mmHg in contralateral non-injected eyes. We observed no significant differences in IOP levels between HSP60 or saline-treated mice. Treatment with HSP60 did not alter visual acuity (VA), contrast sensitivity (CS) or pSTR prior to MB-injection, as compared to saline-treated mice. However, HSP60-treated mice exhibited significantly higher VA and CS as assessed by OMR than saline-treated mice at all time-points after MB-injection. Consistently, RGC function as assessed by pSTR was also significantly improved in HSP60-treated mice compared to saline-treated mice at all time-points after MB-injection.
Immune tolerance to HSP60 attenuates sustained RGC loss and functional loss in our model of glaucoma. Future studies will focus on the mechanism of attenuation of RGC loss through HSP60-specific tolerance.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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