Steroid-Induced Ocular Hypertension (SIOHT) Model using Human Organ-Cultured Anterior Segment (HOCAS)

Abstract

Purpose : Glucocorticoid (GC) has been the mainstay for the management of inflammatory eye diseases. Chronic use of GC induces ocular hypertension (OHT) and also glaucoma in susceptible individuals (steroid responders). However, the molecular basis for such responsiveness is not clearly understood. Therefore, the objective of the present study was to establish SIOHT ex vivo model and to investigate the molecular mechanism that governs steroid responsiveness in human eyes.

Methods : HOCAS was established with paired or single human donor eyes. Intraocular pressure (IOP) was monitored for every 24 h post dexamethasone (DEX) (100/500 nM) or 0.1% ethanol treatment for 7 days after a stable baseline pressure. Myocillin and Fibronectin levels were assayed in conditional media by ELISA.

Results : In 100nM group, DEX treated eyes showed significant elevated IOP in 2/8 eyes (Mean ±SD - mΔIOP: 15.6±0.18; range: 9.6-18 mmHg; 25% responders). Vehicle treated eyes showed mean±SD - mΔIOP of 0.75±0.91 mmHg (range: 0.4-2.3 mmHg). Treatment with 500nM DEX showed significant elevated IOP in 6/8 eyes (Mean ±SD - mΔIOP: 12.5±3; range: 9.6-18 mmHg; 75% responders). Vehicle treated eyes showed mean±SD - mΔIOP of 1.9±1.7 mmHg (range: 0.7-4.9mmHg). DEX inducible proteins such as myocillin and fibronectin levels in conditioned media showed no correlation with elevated IOP. However, the other markers such as α-SMA and collagen IA showed high positivity in HOCAS-TM of responder eyes.

Conclusions : SI-OHT model is fast and reliable to investigate the molecular mechanism involved in the pathogenesis and to screen newer molecules for the management of SI-glaucoma.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.