June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Pathogenesis of Space Associated Neuro-Ocular Syndrome examined using the Ex-Vivo Human Translaminar Autonomous System
Author Affiliations & Notes
  • Tasneem Putliwala Sharma
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Footnotes
    Commercial Relationships   Tasneem Sharma, None
  • Footnotes
    Support  Translational Research Institute for Space Health through NASA Cooperative Agreement NNX16AO69A
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2678. doi:
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      Tasneem Putliwala Sharma; Pathogenesis of Space Associated Neuro-Ocular Syndrome examined using the Ex-Vivo Human Translaminar Autonomous System. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2678.

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

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Abstract

Purpose : The chronic dysregulation between intracranial pressure (ICP) and intraocular pressure (IOP) in space may restructure the posterior eye to a condition that is maladaptive to Earth and can cause Space Associated Neuro-ocular Syndrome (SANS). We will employ our novel ex-vivo translaminar autonomous system (TAS) to effectively recreate the ex-vivo mechanical and pathological IOP/ICP microenvironment to study SANS pathogenesis.

Methods : To recapitulate SANS conditions, dissected human posterior cups (PCs) (N=3) were cultured in the TAS model for various translaminar differentials (IOP: ICP chambers; 16:12; 16:15, 21:12, 21:15 mmHg) and maintained over 14 days. In addition, the ONs were placed in 6- and 10-degree tilts with IOP: ICP at 16:15 mmHg. Posterior globe changes were determined via photomicrographs. We identified retinal, inflammatory and apoptotic markers through TAQMAN arrays. The FN and COLIV expression were examined from conditioned medium of various groups by Western analysis. Degeneration of ON axons from various experimental conditions was assessed by paraphenylenediamine staining. The morphological reorganization and gliosis of optic nerve head (ONH) was studied by expression of LAM and GFAP. TUNEL staining was used to assess apoptosis. Transport and functional analyses were performed by Cholera-toxin B and electroretinograms respectively.

Results : We successfully maintained all translaminar differentials (N=3) over 14 days. Post culture, visual micrograph depicted a general bulging at the ONH for all groups. The 6-degree tilts with IOP: ICP at 16:15 mmHg had elevated expression of all retinal markers compared to control. The tilting of the ON caused highest increase in GFAP, BAX and TLR4 expression. Compared to control, all groups displayed elevated FN and COLIV. Experimental conditions depicted greater degenerated axons. Extensive glial scarring and cupping was also observed due to ON tilting. Increased TUNEL positive cells were identified within experimental groups. Minimal expression of CTB was detected within control and certain experimental groups. Compared to control, ERGs from experimental groups showed varying amplitudes at 1000mcd.s/m2.

Conclusions : Our novel TAS model characterized the SANS pathogenesis. This model can be utilized for future preclinical studies and a unique tool to test new therapeutics that can target SANS pathogenesis in astronauts.

This is a 2021 ARVO Annual Meeting abstract.

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