Dark-phase Intraocular Pressure Elevation and Retinal Ganglion Cell Loss in Experimental Glaucoma

Abstract

 

Purpose:

 

To investigate whether trabecular laser photocoagulation induces dark-phase intraocular pressure (IOP) elevation and retinal ganglion cell (RGC) loss in rats.

 

Methods:

 

Approximately 200 laser burns were delivered to 270° or 330° of trabecular meshwork in adult Brown Norway rats. Light- and dark-phase IOP was measured with the TonoLab tonometer twice weekly up to 5 weeks after laser photocoagulation. To quantify RGC survival, topographic analysis of Rbpms immunolabeling was performed on retinal whole mounts. Grading of axonal injury at the optic nerves and retrograde labeling with Fluorogold were compared.

 

Results:

 

The average awake IOP in the dark and light phases was 32.0±5.2 and 18.8±2.1mmHg, respectively. Both dark and light IOP was dramatically increased for the first week after both laser treatments at 270° and 330° of trabecular meshwork. Then, dark IOP remained elevated up to 5 weeks but light IOP returned to baseline levels. After 270° laser treatment, the average dark and light IOP was 38.4±3.4mmHg and 20.3±2.3mmHg respectively, and the cumulative IOP elevation was 219±82mmHg.day during a 5-week period. This laser treatment elevated dark IOP only (n=10; P<0.001) and did not cause axonal injury. Laser delivered to 330° of trabecular meshwork increased the average dark IOP to 50.7±9.3mmHg by approximately 58% (P=0.003) when compared to contralateral controls, and the cumulative IOP elevation was 466±226mmHg.day during a 5-week period. The density of Rbpms immuno-positive cells was significantly decreased by 26% (n=7; P=0.024). Double labeling analysis showed that 99.5±1.2% of Fluorogold positive cells were Rbpms immuno-positive and 99.3±1.1% of Rbpms immuno-positive cells was labeled with Fluorogold (n=10) indicating RGC loss 5 weeks after laser photocoaulgation at 330° of trabecular meshwork.

 

Conclusions:

 

Our findings demonstrate that laser photocoagulation of a partial trabecular meshwork circumference (330°) increases the level of dark IOP and induces RGC loss in experimental glaucoma.

 

Keywords: intraocular pressure • ganglion cells • optic nerve