July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Immune tolerance to HSP60 attenuates neurodegeneration in a mouse model of glaucoma
Author Affiliations & Notes
  • Eric F. Thee
    Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Kin-Sang Cho
    Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States
  • Martine J. Jager
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Dong Feng Chen
    Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Eric Thee, None; Kin-Sang Cho, None; Martine Jager, None; Dong Chen, None
  • Footnotes
    Support  NIH/NEI R01EY025259, P30EY03790, and Lion’s Foundation grant
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6142. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      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.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×