Abstract
Purpose :
SPARC (secreted protein, acidic, cysteine rich) is a matricellular protein involved in regulation of extracellular matrix, cell adhesion, migration and collagen I deposition. Previous studies show that SPARC null (KO) mice exhibit lower intraocular pressure (IOP) and a more uniform outflow than wild-type (WT) mice. This study investigated the effects of SPARC deletion on aqueous humor dynamics (AHD) in aging mice.
Methods :
Studied were SPARC WT and KO mice of 3 age groups (a, 4-8 weeks; b, 3-5 months; c, 20-28 months). AHD included IOP by rebound tonometer, aqueous flow (Fa) by a modified fluorophotometer and outflow facility (C) by a multi-level constant pressure perfusion method. Anterior segment optical coherence tomography (AS-OCT) was used to measure central corneal thickness (CCT) and anterior chamber depth (ACD). AS-OCT images were segmented semi-automatically to determine the volumes of the cornea (Kv) and anterior chamber (ACv). Unpaired t-tests and ANOVA were used to compare differences among strains and age groups respectively.
Results :
Refer Table 1 for a complete description of results. Key findings include; 1. Lower IOP in young KO mice compared to WT counterparts. This difference is lost with aging, 2. Thicker central corneas in young KO mice, 3. Absence of aging associated reduction in Fa in KO mice.
Conclusions :
SPARC deletion abrogates the normal aging changes seen in WT mice, namely a decrease in aqueous flow, increase in outflow facility, AC deepening and an increase in CCT that maintains IOP unchanged in the WT animals. Absence of these aging changes along with cataract development in all KO mice eventually fails to keep IOP lower than in WT mice. In KO mice, an increase in ACv with no accompanying changes in ACD indicates that the peripheral AC might be widening secondary to loss of lens volume from leaky mature cataracts. The lower IOP of young SPARC KO mice cannot be explained by outflow facility or by corneal changes. Since collagen I is a major structural component of the cornea and sclera, biomechanical factors might affect measured IOP. These findings support the conclusion that SPARC plays a role in normal physiologic changes that maintains IOP with aging.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.