How curcumin affects hyperglycemia-induced optic nerve damage: A short review.

Considered to be one of the most important non-contagious systemic diseases worldwide, diabetes mellitus is still a topical issue on the health agenda with the problems it causes. Exposure to long-term hyperglycemia causes diabetic complications (diabetic neuropathy, nephropathy and retinopathy). The optic nerve can suffer damage by both diabetic retinopathy and neuropathy during diabetes, both because it is formed by axons of retinal ganglion cells and these axons belong to the central nervous system. The issue of hyperglycemia on the optic nerve have been described as diabetic papillopathy, posterior ischemic optic neuropathy, nonarteritic anterior ischemic optic neuropathy and optic atrophy in clinical studies. Experimental studies indicated axon-myelin degeneration in addition to microvascular and ultrastructural changes caused by the hyperglycemia-induced optic nerve damage. Although there are several proposed biochemical mechanisms to cause these damages, oxidative stress emerges as an important factor among them. Oxidative stress leads to pathological state on the nerve cells by affecting the DNA, protein and lipids at different levels. These are causing deterioration on nerve conduction velocity, myelin sheath and nerve structure, neurotrophic support system, glial cells and nerve function. Curcumin, as an important antioxidant, can be an ideal prophylactic agent to eliminate damages on optic nerve. Curcumin helps to regulate the balance of antioxidant and reactive oxygen species by targeting various molecules (NF-κB, STAT3, MAPK, Mfn2, Nrf2, pro-inflammatory cytokines). In addition, it shows healing or preventive effects on myelin sheath damage via regulating ferritin protein in oligodendrocytes. It is also effective in preventing neurovascular damage.

Protective Efficacy of a Dietary Supplement Based on Forskolin, Homotaurine, Spearmint Extract, and Group B Vitamins in a Mouse Model of Optic Nerve Injury.

Glaucoma is a multifactorial blinding disease with a major inflammatory component ultimately leading to apoptotic retinal ganglion cell (RGC) death. Pharmacological treatments lowering intraocular pressure can help slow or prevent vision loss although the damage caused by glaucoma cannot be reversed. Recently, nutritional approaches have been evaluated for their efficacy in preventing degenerative events in the retina although mechanisms underlying their effectiveness remain to be elucidated. Here, we evaluated the efficacy of a diet supplement consisting of forskolin, homotaurine, spearmint extract, and vitamins of the B group in counteracting retinal dysfunction in a mouse model of optic nerve crush (ONC) used as an in vivo model of glaucoma. After demonstrating that ONC did not affect retinal vasculature by fluorescein angiography, we determined the effect of the diet supplement on the photopic negative response (PhNR) whose amplitude is strictly related to RGC integrity and is therefore drastically reduced in concomitance with RGC death. We found that the diet supplementation prevents the reduction of PhNR amplitude (p < 0.001) and concomitantly counteracts RGC death, as in supplemented mice, RGC number assessed immunohistochemically is significantly higher than that in non-supplemented animals (p < 0.01). Major determinants of the protective efficacy of the compound are due to a reduction of ONC-associated cytokine secretion leading to decreased levels of apoptotic markers that in supplemented mice are significantly lower than in non-supplemented animals (p < 0.001), ultimately causing RGC survival and ameliorated visual dysfunction. Overall, our data suggest that the above association of compounds plays a neuroprotective role in this mouse model of glaucoma thus offering a new perspective in inflammation-associated neurodegenerative diseases of the inner retina.

Electrical brain stimulation induces dendritic stripping but improves survival of silent neurons after optic nerve damage.

Repetitive transorbital alternating current stimulation (rtACS) improves vision in patients with chronic visual impairments and an acute treatment increased survival of retinal neurons after optic nerve crush (ONC) in rodent models of visual system injury. However, despite this protection no functional recovery could be detected in rats, which was interpreted as evidence of "silent survivor" cells. We now analysed the mechanisms underlying this "silent survival" effect. Using in vivo microscopy of the retina we investigated the survival and morphology of fluorescent neurons before and after ONC in animals receiving rtACS or sham treatment. One week after the crush, more neurons survived in the rtACS-treated group compared to sham-treated controls. In vivo imaging further revealed that in the initial post-ONC period, rtACS induced dendritic pruning in surviving neurons. In contrast, dendrites in untreated retinae degenerated slowly after the axonal trauma and neurons died. The complete loss of visual evoked potentials supports the hypothesis that cell signalling is abolished in the surviving neurons. Despite this evidence of "silencing", intracellular free calcium imaging showed that the cells were still viable. We propose that early after trauma, complete dendritic stripping following rtACS protects neurons from excitotoxic cell death by silencing them.

Neuroprotective effect of transpupillary thermotherapy in the optic nerve crush model of the rat.

PURPOSE: Transpupillary thermotherapy (TTT) has been shown to induce heat shock protein (Hsp) 72 in optic nerve head tissue. The neuroprotective effect of TTT was investigated in an optic nerve crush rat model. METHODS: TTT was performed onto the optic nerve head in the right eye of subject rats. After 24 h, an optic nerve crush injury using an aneurysm clip was performed at 2 mm from the optic nerve head for 60 s. At 7 and 14 days later, retrograde labelling of retinal ganglion cells (RGCs) with DTMR crystal was carried out and the density of the surviving RGCs was evaluated. Immunohistochemical staining was performed to confirm the expression of Hsp72. RESULTS: At 7 days after optic nerve crush injury, the mean density of surviving RGCs was higher in TTT group (372.7+/-149.8 per mm(2)) than in optic nerve crush group (252.9+/-96.7 per mm(2)) with borderline significance. In the retinal areas at 1 mm from the optic nerve head, a significant increase in surviving RGCs from TTT treated eyes was observed at both 7 and 14 days after optic nerve crush injury. However, no significant differences in surviving RGCs were demonstrated 2 and 3 mm from the optic nerve head. CONCLUSIONS: These results demonstrate that TTT aimed onto the optic nerve head showed a neuroprotective effect.

Optic nerve massaging: an extremely rare cause of self-inflicted blindness.

PURPOSE: To report a patient whose self-inflicted blindness was not clinically apparent by history or external signs of trauma. DESIGN: Observational case report. METHODS: A 12-year-old girl with a history of social and behavioral problems was noted to have visual loss in her right eye. Examination revealed no light perception, optic nerve atrophy, partial upper lid ptosis, exotropia, and hypoesthesia of the cheek, all on her right side. RESULTS: After undergoing extensive examinations which were unrevealing for a diagnosis, the patient admitted to a recurrent maneuver, which she secretly used to relieve anxiety and stress. This maneuver consisted of inserting her index finger under the right supraorbital rim and forcibly subluxating her globe out of the orbital space. CONCLUSIONS: Self-inflicted visual loss can occur in nonpsychotic and nonviolent patients. Accurate diagnosis is important, as there is a risk of similar involvement to the fellow eye, and referral for psychiatric counseling is mandatory.