Retinal Degeneration Is Being Mediated Through Cistauosis upon Optic Nerve Crush in Mouse Models
سال انتشار: 1397
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 565
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شناسه ملی سند علمی:
IRAVOMED08_075
تاریخ نمایه سازی: 21 اردیبهشت 1397
چکیده مقاله:
Purpose: Tau abnormal hyperphosphorylation is one of the major pathological hallmarks in retinal disorders including traumatic optic nerve and glaucoma. Despite of extensive consideration it remains uncertain how tau dysfunction contributes to retinopathy. It has been reported that phosphorylated tau at Th231 exists in the two distinct cis and trans conformation which that cis is extremely neurotoxic and is the early driver of tauopathy and neurodegeneration. Thus, we hypothesized that cis p-tau could be the central mediator of neural cell death upon retinopathy Methods: To examine the cis p-tau mediatory role, we initially modeled the mice and then immunostained optic nerve and retinal sections as well as whole retina in various time points (1h, 6h, 24h, 3d, 12d and 21d post crush).Results: We have found a remarkable increase in cis p-tau levels acutely after crush, which in turn disrupts axonal microtubule network, spreads to other neurons, and leads to apoptosis, a pathogenic process which was termed cistauosis . Also, we observed prominent cis p-tau accumulation in whole retina at 21nd days post injury. It is notable that we observed cis-p tau at the earliest 24 hours of crush but not sooner than the point.Conclusion: These results demonstrate cistauosis as an early pathogenic process of neurodegeneration upon retinopathy and would have profound implications for finding efficient therapeutic strategies
نویسندگان
Sara Poosty
Royan Institute for Stem Cell Biology and Technology
Zahra Seiedrazizadeh
Royan Institute for Stem Cell Biology and Technology
Koorosh Shahpasand
Royan Institute for Stem Cell Biology and Technology
Hossein Baharvand
Royan Institute for Stem Cell Biology and Technology