Glial Changes and Role of Connexin43 in a Laser-induced Rodent Model of Retrobulbar Optic europathy

Abstract

Purpose: To establish a novel model of rodent optic nerve damage in order to investigate glial changes occurring in retrobulbar portion of the optic nerve after the injury and to facilitate development of neuroprotective agents. Methods: Rats (200-250g) were first anaesthetised via intraperitoneal approach with a mixture of Xylazine and Ketamine. An incision was made through superior conjunctiva and Tenon’s capsule and orbital portion of the optic nerve exposed. Argon green laser (514nm) with 50mW power was shone for 30 sec on the retrobulbar portion of the optic nerve immediately posterior to the globe. Animals were left alive for variable number of days post induction of neuropathy. Haematoxylin and eosin as well as variety of immunohistochemichal stains have been used to investigate glial changes in the optic nerve at different time points after the injury. Connexin43 Antisense Oligodeoxynucleotide has been investigated as a potential neuroprotective agent following the optic nerve injury. Results: Glial changes have been documented following laser-induced injury to the optic nerve. No optic nerve head swelling has been observed at any time point after the injury. There was no statistically significant increase in lesion size between different time points. Significant inflammatory response was observed in the optic nerve from early time points after the injury through to the last follow up at one month. Connexin43 was shown to have a prominent role in glial inflammatory changes in the optic nerve following laser-induced retrobulbar optic neuropathy. Connexin43 Antisense Oligodeoxynucleotide was not effective in reducing the size of the lesion or modifying inflammatory response in the damaged optic nerves. Conclusion: A novel model of rodent retrobulbar optic neuropathy has been established with well documented glial changes at different time points after the injury. Connexin43 plays an important role in early as well as late inflammatory response to injury in the retrobulbar portion of the optic nerve.