Imipramine protects retinal ganglion cells from oxidative stress through the tyrosine kinase receptor B signaling pathway

Retinal ganglion cell（RGC） degeneration is irreversible in glaucoma and tyrosine kinase receptor B（Trk B）-associated signaling pathways have been implicated in the process.In this study,we attempted to examine whether imipramine,a tricyclic antidepressant,may protect hydrogen peroxide（H_2O_2）-induced RGC degeneration through the activation of the Trk B pathway in RGC-5 cell lines.RGC-5 cell lines were pre-treated with imipramine 30 minutes before exposure to H_2O_2.Western blot assay showed that in H_2O_2-damaged RGC-5 cells,imipramine activated Trk B pathways through extracellular signal-regulated protein kinase/Trk B phosphorylation.TUNEL staining assay also demonstrated that imipramine ameliorated H_2O_2-induced apoptosis in RGC-5 cells.Finally,Trk B-Ig G intervention was able to reverse the protective effect of imipramine on H_2O_2-induced RGC-5 apoptosis.Imipramine therefore protects RGCs from oxidative stress-induced apoptosis through the Trk B signaling pathway.

Electrical stimulation scheme optimization for retinal prosthesis:considerations from biological perspective

Effective and safe electrical stimulation of the retinal ganglion cells is at the heart of retinal prosthesis design.However,the effectiveness and safety demand of the electrical stimulation is often at odds against each other.Besides,the nerve fiber layer above retinal ganglion cells limits the spatial resolution of stimulation.Also,current retinal prosthesis still cannot selectively activate the ON or OFF visual pathways,thus cannot relay the correct luminance information to the brain.With decades of development,the stimulation protocol for retinal implants began to tackle these problems.We believe that a novel design of electrical stimulation scheme,combined with gene therapy technique,can improve the selectivity and spatial resolution of retinal implants and further lower the damage caused by electric stimulation.

Glaucomatous optic neuropathy treatment options:the promise of novel therapeutics,techniques and tools to help preserve vision

Peripheral vision loss followed by ＂tunnel vision＂ and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma（POAG） and normotensive glaucoma（NTG）.These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells（RGCs） accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve.Since patients suffering from this glaucomatous optic neuropathy（GON） first notice visual impairment when they have lost 〉 40% of their RGCs,early diagnosis is the key to retard the progression of glaucoma.Elevated intraocular pressure（IOP）,low cerebrospinal and/or low intracranial fluid pressure,advancing age,and ethnicity are major risk factors associated with POAG.However,retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic,inflammatory,oxidative and mechanical insults also contribute to vision loss in POAG/GON.Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs,combination drug products,and surgical interventions.Two recently approved multi-pharmacophoric drugs（e.g.,rho kinase inhibitor,Netarsudil;a drug conjugate,Latanoprostene Bunod） and novel aqueous humor drainage devices（i Stent and Cy Pass） are also gaining acceptance for treating POAG/NTG.Neuroprotective and regenerative agents,coupled with electroceutical,mechanical support systems,stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON.The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures,thereby providing a gain of function of the visual system for the glaucoma patients.

Neuroprotective effect of recombinant human erythropoietin on optic nerve injury in rats

Background Optic nerve injury, caused by retinal and optic nerve diseases, can eventually result in vision loss. To date, few effective treatments have been discovered to restore visual function. Previous studies showed that recombinant human erythropoietin （rhEPO） has a neuroprotective effect on the central nervous system, particularly in nerve injury. In this study, we investigated the effects of rhEPO on axonal regeneration and functional restoration following optic nerve injury. This was done by measuring the expression of growth associated protein 43 （GAP-43）, a marker for neuronal regeneration, on the retina and flash-visual evoked potential （F-VEP）. Methods Adult Wistar rats were randomly assigned to rhEPO and control （saline） groups. Optic nerve crush injury models were established and rhEPO or saline were immediately injected into the vitreous cavity. The expression of GAP-43 was detected by immunohistochemistry and the F-VEP was measured pre-injury, immediately after injury, 1 week and 2 weeks post-injury. Results No detectable staining for GAP-43 was observed in normal retina. In the control group, the level of GAP-43 expression was higher at 1 week post-injury, but decreased at 2 weeks. In the rhEPO group, the level of GAP-43 expression was notably higher at both 1 week and 2 weeks. At each time point post-injury, the expression of GAP-43 in rhEPO group was significantly higher than the control group （P 〈0.05）. Obvious changes in F-VEP examination were detected immediately after optic nerve injury, including significantly prolonged latency and decreased amplitude of the P1 wave. In the control group, the changes were still obvious at 1 week. The latency was decreased and the amplitude had slightly recovered to 28.23% of the normal value at 2 weeks. In rhEPO group, there was significantly more recovery than the control group at 1 week and 2 weeks post-injury （P 〈0.05）. The latency most close to the normal level and the amplitude had recovered to 65.51% of the normal value at 2 weeks. Conclusions rhEPO can prolong the expression of GAP-43 and increase its intensity after optic nerve injury, thereby promoting neural repair and axonal regeneration. Under the protection of rhEPO, the conduction velocity of the optic nerve recovered significantly. Therefore, rhEPO has neuroprotective effects on the optic nerve and promotes functional restoration of the optic nerve. Chin Med J 2009;122（17）：2008-2012

Advances in optic nerve regeneration and neuroprotection strategies

The most common irreversible blindness diseases are age-related macular degeneration, glaucoma, anddiabetic retinopathy which involve the optic nerve or retina. These diseases share a common condition of causing blindness - progressive neural cells loss of retina （photoreceptor ceils, retinal ganglion cells （RGCs））. Although many advances in the treatment for these diseases have been achieved in recent years, the visual function often cannot be reversed. To improve the visual outcomes, the retinal neuron cells must be rescued. Optic nerve diseases including glaucoma were mostly studied for the effort to rescue the injured neurons and regenerate the neuron axons.