June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Adeno-associated virus Type 2-mediated Expression of HSPB1 Protects Retinal Ganglion Cells against Ocular hypertension in Mice
Author Affiliations & Notes
  • Mihyun Nam
    Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Armaan Dhillon
    Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Rooban B Nahomi
    Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Mina B Pantcheva
    Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Ram H Nagaraj
    Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Footnotes
    Commercial Relationships   Mihyun Nam None; Armaan Dhillon None; Rooban Nahomi None; Mina Pantcheva None; Ram Nagaraj None
  • Footnotes
    Support  SPARK/REACH
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1615 – A0438. doi:
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    • Get Citation

      Mihyun Nam, Armaan Dhillon, Rooban B Nahomi, Mina B Pantcheva, Ram H Nagaraj; Adeno-associated virus Type 2-mediated Expression of HSPB1 Protects Retinal Ganglion Cells against Ocular hypertension in Mice. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1615 – A0438.

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

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Abstract

Purpose : To investigate the protective effect of adeno-associated virus type 2 (AAV2)-mediated expression of HSPB1 in retinal ganglion cells (RGCs) against ocular hypertension-induced RGC death in mice.

Methods : We constructed an AAV2 vector encoding human HSPB1 with a mini RGC-specific neurofilament light chain promoter PLE345 for specific expression in RGCs. Microbeads were injected into the anterior chamber of mice two weeks before or two weeks after the AAV2-HSPB1 injection. IOP was measured using a tonometer. Retinal flatmounts were fixed and immunostained for RGCs and activated microglia with specific antibodies. Anterograde axonal transportation was assessed by intravitreal injection with Alexa fluor-555 conjugated cholera toxin-B subunit (CTB).

Results : Intravitreal injection of AAV2-HSPB1 resulted in robust expression of HSPB1 in both the soma and axons of RGCs. The IOP was significantly elevated one week after microbeads injection. The microbead-injected mice showed a gradual decrease in RGCs, with a 36% decrease at six weeks post-injection. AAV2-HSPB1 administration one week after microbead injection resulted in significant prevention of RGC loss, with only a 12% decrease at six weeks. The microbead-injected mice showed defective anterograde transportation of CTB along the length of the optic nerve. The AAV2-HSPB1 administration inhibited these axonal defects. In addition, the administration of AAV2-HSPB1 prevented the activation of microglia in microbead-injected mice.

Conclusions : Intravitreal administration of AAV2-HSPB1 resulted in RGC-specific expression of HSPB1. HSPB1 expression protected RGC somas and axons in mice with ocular hypertension. Our results suggest that AAV2-HSPB1 could be advanced as a therapy for neuroprotection in glaucoma.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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