7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection

To analyze the neuroprotective effects of 7,8-Dihydroxyflavone (DHF) in vivo and ex vivo, adult albino Sprague-Dawley rats were given a left intraorbital optic nerve transection (IONT) and were divided in two groups: One was treated daily with intraperitoneal (ip) DHF (5 mg/kg) (n = 24) and the other (n = 18) received ip vehicle (1% DMSO in 0.9% NaCl) from one day before IONT until processing. At 5, 7, 10, 12, 14, and 21 days (d) after IONT, full field electroretinograms (ERG) were recorded from both experimental and one additional naïve-control group (n = 6). Treated rats were analyzed 7 (n = 14), 14 (n = 14) or 21 d (n = 14) after IONT, and the retinas immune stained against Brn3a, Osteopontin (OPN) and the T-box transcription factor T-brain 2 (Tbr2) to identify surviving retinal ganglion cells (RGCs) (Brn3a+), α-like (OPN+), α-OFF like (OPN+Brn3a+) or M4-like/α-ON sustained RGCs (OPN+Tbr+). Naïve and right treated retinas showed normal ERG recordings. Left vehicle-treated retinas showed decreased amplitudes of the scotopic threshold response (pSTR) (as early as 5 d), the rod b-wave, the mixed response and the cone response (as early as 10 d), which did not recover with time. In these retinas, by day 7 the total numbers of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs decreased to less than one half and OPN+Brn3a+RGCs decreased to approximately 0.5%, and Brn3a+RGCs showed a progressive loss with time, while OPN+RGCs and OPN+Tbr2+RGCs did not diminish after seven days. Compared to vehicle-treated, the left DHF-treated retinas showed significantly greater amplitudes of the pSTR, normal b-wave values and significantly greater numbers of OPN+RGCs and OPN+Tbr2+RGCs for up to 14 d and of Brn3a+RGCs for up to 21 days. DHF affords significant rescue of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs, but not OPN+Brn3a+RGCs, and preserves functional ERG responses after IONT.

Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection

Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X7 receptors and Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma.

Lycium barbarum (Wolfberry) Increases Retinal Ganglion Cell Survival and Affects both Microglia/Macrophage Polarization and Autophagy after Rat Partial Optic Nerve Transection

The rat partial optic nerve transection (PONT) model has been used for studying secondary degeneration of retinal ganglion cells (RGCs) in recent years. In this study, we carried out PONT of the temporal side of rat optic nerves, whereas PONT was carried out of the superior side in the previous publication. We found that this surgery is better and easier than the previous method and can produce a repeatable and reliable model. We detected significant changes in the polarization of microglia/macrophages and the level of autophagy in optic nerves after PONT. We also used this model to detect the effects of the polysaccharides extracted from Lycium barbarum (LBP) on the survival of RGCs and the changes in the polarization of microglia/macrophages and the level of autophagy after PONT. We find that LBP can delay secondary degeneration of RGCs after temporal injury of optic nerves, promote the M2 polarization of microglia/macrophages, and down-regulate the level of autophagy after PONT. In conclusion, we find that the polarization of microglia/macrophages and the autophagy level change after PONT; LBP treatment delays secondary degeneration of RGCs; and the polarization of microglia/macrophages and the level of autophagy are also altered after LBP treatment.

Traumatic Luxation of the Eye Ball with Optic Nerve Transection Following Road Traffic Accident: Report of Two Cases and Brief Review of Literature

Background: Traumatic luxation of the eye ball is rare with only 106 cases reported in PubMed till date. The anatomic location of the eyeball within the socket and the resilience of the globe to pressure force, attachment to extraocular muscles and optic nerve prevents luxation during trauma. Case: Road traffic accidents (RTA) is the most common cause for these injuries and the outcome can vary from complete recovery on repositioning to visual loss due to globe perforation or optic nerve injury. We report two unique cases of traumatic right globe luxation and complete optic nerve transection due to RTA and give a brief review of literature. Conclusion: RTA leading to eye ball luxation though rare can be a challenging situation when encountered. Given the limited time for the salvage of the eye early intervention is not always possible especially in developing countries where there is delay in reaching the hospital. Despite all these confounding factors attempt must be made to salvage the eye either for functional, cosmetic or psychological reasons.