Abstract
Purpose :
Thrombospondin-1 (TSP1) is a matricellular protein that is expressed in the trabecular meshwork, and its expression increases in glaucoma patients. TSP1-deficient mice were found having lower IOP in a previous study. This study aimed to investigate whether IOP elevation can be inhibited in TSP1-deficient mice using a steroid-induced ocular hypertension (SIOH) mouse model.
Methods :
TSP1-deficient mice (N=14) and wild type (WT) mice (N=14), both including equal males and females, were randomly divided into saline-treated and dexamethasone (DEX)-treated groups (4 groups in total, n=7/group). Both eyes of each mouse received 10μl of saline or 0.1% DEX eye drops respectively twice a day for 5 weeks. IOP was measured weekly. IOP data were analyzed with both Student’s t-test and Three-way ANOVA with repeated measurements.
Results :
TSP1-deficient mice showed a ~2mmHg lower IOP at the baseline (p<0.001) when compared to WT mice, and this difference remained consistent between two saline-treated groups for 5 weeks. DEX treatment significantly elevated IOP in week1 (p<0.001) and peak IOP occurred at week 4 in WT mouse eyes compared to the saline-treated group. However, in TSP1-deficient mice, DEX did not induce a significant increase in IOP until week2 and the peak of IOP was at week2. The mean DEX-induced elevation in IOP was 3.4mmHg at week1, 5.6mmHg at week2, and 5.9mmHg at week5 in WT mice, while 0.2mmHg at week1, 2.2mmHg at week2, and 1.1mmHg at week5 in TSP1-dificient mice. The mean percentage increase in IOP induced by DEX over saline-treated control was 25% at week1, 41% at week2, and 42% at week5 in WT mice, while 3% at week1, 19% at week2, and 9% at week5. Therefore, DEX-induced increase in IOP was a half in TSP1-deficient mice when compared to WT mice at week2, and about 1/4 at week5. Three-way ANOVA also showed a significant main effect of the genotype (p<0.0001) and significant interactions of both genotype X treatment (p<0.0001) and genotype X time (p<0.0001).
Conclusions :
TSP1 deficiency showed significant inhibitory effects on DEX-induced IOP elevation in mouse eyes. These effects included the delayed start-point of IOP elevation, lower peak IOP increase, and unsustainable IOP elevation. Our data suggest that TSP1 may play a role in SIOH. The mechanisms of its inhibition effects and morphological association in the outflow pathway need to be elucidated in further studies.
This is a 2021 ARVO Annual Meeting abstract.