Abstract
Purpose :
The chronic dysregulation between intracranial pressure (ICP) and intraocular pressure (IOP) in space may readapt the optic nerve head, lamina cribrosa, and optic nerve (ON) subarachnoid space to a condition that is maladaptive to Earth and can cause Space Associated Neuro-ocular Syndrome (SANS) (2). We will employ our novel ex-vivo translaminar autonomous system (TAS) to recreate the ex-vivo mechanical and pathological IOP/ICP microenvironment. To this end, we hypothesize that the ex-vivo human translaminar autonomous system will be an effective model to study SANS pathogenesis.
Methods :
To recapitulate the human SANS conditions, dissected human posterior cups (PCs) (N=3) were cultured in the TAS model for 14 days. We independently generated translaminar pressure gradient (TLPG) differentials by raising the media reservoir connected to IOP and ICP chambers to different heights (hydrostatic pressures; IOP: ICP; 16:12; 16:15, 21:12, 21:15 mmHg) and maintained pressure differentials over time. In addition, the ONs were placed in 6- and 10-degree tilts with IOP: ICP at 16:15 mmHg). We determined the architecture, thickness and structure of the retinal nerve fiber layer, optic nerve head and globe by optical coherence tomography, immunohistochemistry, and software analysis as an imaging tool. The PCs were stained for extracellular components (COL4A1, LAM) and inflammatory markers (GFAP, TLR4, TNFa).
Results :
The TAS model allowed autonomous regulation of pressure in both chambers. We maintained TLPG differentials (IOP: ICP; IOP: ICP; 16:12; 16:15, 21:12, 21:15 mmHg) (N=3) over 14 days. Post culture in the model, the PCs stained positive for COL4A1, LAM, and GFAP. Significant pathogenic morphological changes were observed in the PCs under various conditions over time.
Conclusions :
Our novel TAS model will allow us to effectively characterize the TAS model and analyze ICP as a crucial factor for 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 2020 ARVO Annual Meeting abstract.