Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat.
ABSTRACT Citicoline and lithium (Li(-)) have been shown to support retinal ganglion cell (RGC) survival and axon regeneration in vitro. Optic nerve crush (ONC) is a model of both brain axonal injury and certain aspects of the glaucomatous degeneration of RGC. We have used this model to quantify protection offered to RGC by these drugs and to determine whether their effects are mediated by enhanced expression of the antiapoptotic protein Bcl-2. Adult rats (6-12 per group) were subjected to ONC accompanied by a contralateral sham operation. Animals were treated intraperitoneally with either vehicle, citicoline sodium (1g/kg daily for up to 7 days and 300 mg/kg daily afterwards), lithium chloride (30 mg/kg daily), or both drugs combined. Fluorogold was injected bilaterally into superior colliculi 1, 5 or 19 days after ONC. Labeled cells were counted under a fluorescence microscope 2 days after tracer injection. In a separate set of experiments the effects of treatments on expression of Bcl-2 in retinas were evaluated by immunohistochemistry. In vehicle-treated animals there was a progressive decrease of RGC density after crush. This decrease was attenuated in citicoline-treated animals 1 week and 3 weeks after the crush. In the lithium-treated group protection was even more pronounced. In animals treated with both drugs RGC protection was similar to that achieved by lithium alone. Bcl-2 immunoreactivity was seen predominantly in retinal ganglion cells. Its increase was recorded in the lithium and citicoline group as well as in animals treated with the combination of both drugs. Both citicoline and lithium protect RGC and their axons in vivo against delayed degeneration triggered by the ONC. Retinoprotective action of both drugs may involve an increase in Bcl-2 expression.
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ABSTRACT: Glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO) are major diseases that can lead to blindness and affect mainly the elderly population worldwide. The results of recent investigations have demonstrated that the death of retinal ganglion cells (RGCs) and their axons is the common pathological change in these three disease processes. The exact mechanism that is responsible for the onset and progression of RGC death and axonal degeneration in patients with glaucoma, DR and RVO has not been definitively determined. Thus, identifying the risk factors for the onset and the progression of RGC neuropathy can help in deciding not only the specific treatments but also whether the treatments should be initiated, withheld, or augmented in individuals with glaucoma, DR, and RVO. This review describes the major risk factors for the onset of glaucoma, and the factors associated with the progression of glaucoma that have been obtained from large population-based prevalence and incidence studies. In addition, the potential risk factors for glaucoma, diabetes mellitus, and RVO are discussed in terms of the results obtained by both clinical and laboratory studies. This review introduces potential neuroprotective therapies for damaged RGC in eyes with RGC neuropathy, and the factors that should be considered for a complete therapy for the RGC neuropathy involved in glaucoma, DR and RVO. Neuroprotective therapies combined with a reduction of the IOP should be considered for the complete management of RGC neuropathy involved in glaucoma, DR and RVO.Clinical and Experimental Ophthalmology 02/2012; S-3. · 1.96 Impact Factor
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ABSTRACT: This study demonstrates that subthreshold transpupillary thermotherapy (TTT) laser irradiation on optic nerve head protects retinal ganglion cells (RGCs) in an optic nerve crush (ONC) model. TTT was performed in right eyes with an 810-nm diode laser aimed at the center of the optic nerve head, using the following protocol: power 60mW, duration 60s, spot size 500mum. Fluoro-Gold was injected into bilateral superior colliculi 5 days before sacrifice and fluorescent gold labeled RGCs were counted under fluorescence microscopy. In the ONC group, a progressive loss of RGCs was observed; however, in comparison with the ONC group, RGCs density was significantly higher (P=0.001, independent samples t-test) at day 7 postoperative and only borderline significances were obtained at days 14 and 28 postoperative (P=0.044 and P=0.045, respectively, independent samples t-test) in ONC+TTT group, which implies the potential neuroprotective role of TTT. This protective effect seems to be heat shock proteins (HSPs) related, because intraperitoneal Quercetin (an inhibitor of HSPs, 4mg/kg/day for 7 days) could completely abolish this protective effect at days 7, 14 and 28 postoperative (P=0.012, P=0.002, and P=0.000, respectively, independent samples t-test). Minimal collateral damage of TTT on optic nerve head tissue, peripapillary RGCs and the myelin sheath of the optic nerve were observed under transmission electron microscopy. These findings suggested that subthreshold TTT might be a safe and practical approach to protect RGCs. The underlying mechanisms may involve TTT-induced HSPs in RGCs.Neuroscience Letters 05/2010; 476(1):3-8. · 2.03 Impact Factor
Article: [Neuroprotective approaches.][Show abstract] [Hide abstract]
ABSTRACT: After introduction of vitreoretinal surgery more than 40 years ago, further development of the procedure involved a continuous reduction of potential toxic effects by irrigating solutions, endoillumination or mechanical manipulation. Recently, additional efforts were made to prevent neurodegeneration via pharmacological intervention. Taurine as additive for irrigating solutions can be considered as an example for neuroprotectants in vitreoretinal surgery. Approval of neuroprotective agents demands an increased effort for preclinical and clinical evaluation. To date, only few neuroprotective substances are used in clinical routine in the context of vitreoretinal surgery, however, experimental data suggest a high potential of various neuroprotective agents. The following article gives an overview of current neuroprotective approaches feasible for vitreoretinal surgery and a critical analysis of their clinical relevance.Der Ophthalmologe 09/2013; · 0.53 Impact Factor