Abstract
Purpose :
Blebs from bleb-forming glaucoma surgeries utilize sub-conjunctival lymphatics for aqueous outflow and intraocular pressure (IOP) reduction. Here, we test the ability to pharmacologically manipulate sub-conjunctival lymphatics as a way to modulate bleb biology
Methods :
Lymphatics are natively visible in reporter mice that express GFP under a Prox-1 promoter. Superior sub-conjunctival injections were performed (vascular endothelial growth factor-C [VEGFC; n=11 at 0.36 mg/ml], mitomycin-C [MMC, n=10 at 0.25 mg/ml and n=9 at 0.5 mg/ml], 5-fluorouracil [5FU; n=10 at; 50 mg/ml]), control (BSS; n=10), and non-injected controls (n=10). Three sub-conjunctival injections were given (every other day), and eye were harvested and fixed in 4% PFA on the 7th day. Anterior segment flat mounts were visualized by fluorescent microscopy. Sub-conjunctival lymphatic length and branch number were quantified. Comparisons were made by Mann-Whitney U test.
Results :
Sub-conjunctival lymphatics were readily visible. Many comparisons were made and main results included increased lymphatic branch number (p=0.007) with trending increase in length (p=0.06) after BSS injection, demonstrating the impact of trauma. VEGFC increase lymphatic length and branch number compared to all conditions (p<0.001-p=0.004). 5FU demonstrated decrease in lymphatic branch number and length (both p=0.015) to BSS control. MMC also demonstrated a significant or trending decrease in lymphatic branch and length (p<0.001-0.075) to BSS control. A mild dose-dependent effect was seen for MMC with trending lesser lymphatic length at the higher dose (p=0.079). These overall changes were further less significant on the temporal/nasal to inferior portions of the eye as the injections were superior.
Conclusions :
Sub-conjunctival lymphatic presence can be pharmacologically manipulated. Enhanced presence may be useful for improving aqueous outflow and IOP reduction after performing bleb-forming glaucoma surgeries. Limiting sub-conjunctival lymphatic presence may improve the sub-conjunctival space as a drug delivery depot by diminishing lymphatic drainage from that space.
This is a 2021 ARVO Annual Meeting abstract.