Abstract
Purpose :
Our laboratory identified stanniocalcin-1 (STC-1) as an IOP-lowering protein when administered topically to mouse models of ocular hypertension. Here, we investigate the IOP lowering effects of intracameral and subconjunctival injection of an adeno-associated virus containing a FLAG- tagged STC-1 transgene (AAV-STC-1-FLAG) in two mouse models of ocular hypertension.
Methods :
Ocular hypertension was established in C57BL/6J mice (6-8 months old) with 5 weekly injections of a dexamethasone-acetate suspension into the conjunctival fornix. Following confirmation of IOP induction with a handheld rebound tonometer, mice received a single injection of subconjunctival AAV-GFP, 6 x 109 viral genomes (VGs, n=7), intracameral AAV-GFP (3 x 109 VGs, n=9), subconjunctival AAV-STC-1-FLAG (6 x 109 VGs, n=8), or intracameral AAV-STC-1-FLAG (3 x 109 VGs, n=9). Steroid injections were maintained for an additional 4 weeks. IOP was assessed twice weekly and averaged over the treatment period (4-6 weeks). To evaluate IOP-lowering effects in a chronic ocular hypertensive model, DBA/2J mice were injected (age 5 months) similarly with subconjunctival (n=14) AAV-GFP in one eye and AAV-STC-1-FLAG in the fellow eye or intracameral (n=15) AAV-GFP in one eye and AAV-STC-1-FLAG in the fellow eye (same concentrations as above). IOP was assessed as described above.
Results :
IOP was reduced in the steroid induced ocular hypertension model with both intracameral (25.4%, 20.3 vs 15.1mmHg, P<0.001) and subconjunctival (19.9%, 18.9 vs 15.2mmHg, P<0.001) AAV-STC-1-FLAG for the 4 week time period. Similar IOP reduction was noted in DBA/2J mice with both intracameral (16.2%, 19.6 vs 16.4mmHg, P=0.01) and subconjunctival (16.6%, 17.2mmHg vs 14.3mmHg, P<0.001) AAV-STC-1 for the 6 week time period.
Conclusions :
AAV-STC-1 lowers IOP in two separate models of ocular hypertension characterized by different mechanisms of outflow obstruction. Both intracameral and subconjunctival administration of AAV-STC-1 lowers IOP in a sustained manner.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.