Neuroprotective Effect of Adenosine on Calibrated Optic Nerve Injury in Rats

Abstract

Abstract: : Purpose: There are several hurdles in the clinical application of neurotrophic factors for retinal disorders in terms of their delivery. This study was conducted to investigate the neuroprotective effect of adenosine, which may elicit actions of neurotrophic factors in the retina, in the calibrated optic nerve injury model. Methods: Fluorogold (FG) was injected to the both superior colliculi of adult rats to label the retinal ganglion cells (RGCs) (Day 0). On Day 7, adenosine (1, 10 and 100 µg) or BDNF (2 µg) in 4µl of PBS or PBS only was intravitreally injected via the posterior root. The other group of rats was given BDNF by instillation at the concentration of 80 µg /mL through Day 5 to 6, three times a day. On Day 7, after the treatment was completed, a calibrated injury was made on the optic nerve (ON) at about 2 mm from the globe by applying an aneurysm clip for 20 seconds. Rats were euthanized on Day 14 (adenosine/BDNF/PBS injection groups) or Day 17 (BDNF instillation group), and RGC survival rates were estimated by counting FG-labeled cells in 12 standard areas of each flat-mounted retina. Results: The densities of labeled RGCs in normal rats were 2518 +/- 219 cells/mm² (mean +/- SD; n=8). In the rats treated with the vehicle only, the mean density was decreased to 43% of that of normal eyes. Treatment with 10 or 100 µg of adenosine significantly prevented the RGC loss compared to the vehicle treatment (mean densities 52% and 55% of normal eyes, respectively). Intravitreous BDNF also significantly prevented the RGC loss (60% of normal eyes), while instillation of BDNF showed less protective effect. Conclusions: Administration of exogenous adenosine has neuroprotective effect against RGC death induced by ON injury. These results suggest potential efficacy of adenosine in treating glaucoma.

Keywords: adenosine • ganglion cells • neuroprotection