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Jin Hyoung Park, Soon-Suk Kang, JINA SHIN, Jeong Hye Sunwoo, Eun Soon Kim, Jae Yong Kim, Hungwon Tchah; Nerve Growth Factor Attenuates Cataract Formation in the Diabetic Lens. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4973. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effects of nerve growth factor (NGF) on apoptosis, inflammation and epithelial-mesenchymal transition (EMT) in the diabetic lens.
To investigate the effects of NGF on glucose-induced apoptosis, we stained human lens epithelial cells (HLECs) using fluorescein isothiocyanate (FITC)-labeled annexin-V and propidium iodide (PI), and measured expression of cleaved caspase-3 and the Bcl-2 by western blot. Moreover, to examine the effects of NGF on inflammation, we quantified the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) using multiplex cytokine analysis, and analyzed nuclear factor-κB (NF-κB) activation and NF-κB inhibitor α (IκB-α) degradation using western blot analysis. And, to investigate the effects of NGF on EMT, we measured expression of α-smooth muscle actin (α-SMA) and vimentin. To investigate the effects in vivo, we induced diabetes in male Sprague–Dawley rats using streptozotocin. The rats were divided into 3 groups: “Control”, “Diabetic control”, and “Diabetic NGF”; topical NGF was applied three times daily for 8 weeks. We used immunohistochemistry to identify cleaved caspase-3, IL-1β and α-SMA.
In HLECs, high glucose concentration (≥ 25 mM) led to apoptosis, the release of inflammatory cytokines and EMT. NGF markedly reduced Annexin-PI-positive cells, and levels of cleaved caspase-3, IL-1β, TNF-α, α-SMA and vimentin and increased Bcl-2 expression. In the diabetic rat lens, apoptosis, inflammation and EMT were enhanced, as were levels of cleaved caspase-3, IL-1 β and α-SMA. These responses were markedly reduced by NGF.
Apoptosis, inflammation and EMT are enhanced in the diabetic lens; NGF attenuates these responses—both in vivo and in vitro. Therefore, NGF therapy may represent a novel approach for the prevention and management of diabetic cataract.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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