Investigative ophthalmology & visual science · 2026
Myd88 Deficiency Accelerates Retinal Degeneration and Alters Microglial Dynamics in a Mouse Model of Retinitis Pigmentosa.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shimokawa Shotaro, Shimokawa Sakurako, Zhao Huanyu, Funatsu Jun, Hisai Takahiro, Yamamoto Kaho, Nakatake Shunji, Fujiwara Kohta, Okita Ayako, Koyanagi Yoshito, Notomi Shoji, Ishikawa Keijiro, Yawata Nobuyo, Yoshida Noriko, Ikeda Yasuhiro, Shibata Kensuke, Sonoda Koh-Hei, Murakami Yusuke
Аннотация
PURPOSE: Neuroinflammation is triggered by the recognition of damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs). Toll-like receptors (TLRs)/MyD88 is the PRR pathway that mediates inflammatory signaling. We investigated the functions of Myd88 in retinal degeneration and neuroinflammation in a mouse model of retinitis pigmentosa (RP).
METHODS: Rd10 mice were crossed with Myd88-/- mice to produce rd10; Myd88-/- mice. The retinal phenotype was assessed by TUNEL, hematoxylin and eosin (H&E) staining, and electroretinography. Retinal microglia were immunostained with Iba-1. Retinal mRNA profiles associated with neuroinflammation were analyzed using a NanoString Neuroinflammation panel.
RESULTS: Myd88 deficiency increased the number of TUNEL-positive cells in the outer nuclear layer (ONL) and exacerbated ONL thinning at postnatal day 18 and 21 (P < 0.01, each). Consistent with these findings, the scotopic electroretinogram (ERG) showed lower b-wave amplitudes in rd10; Myd88-/- mice compared with rd10 mice (P < 0.01). Microglial infiltration into the outer retina showed an early but transient increase at P18, followed by a reduction at P21 in rd10; Myd88-/- mice. Retinal mRNA profiling revealed increased expression of Ifitm3 and Serpina3n, markers of astrocytic glia, in rd10; Myd88-/- mice. Immunostaining confirmed the upregulation of IFITM3 and SERPINA3N in astrocytes and Müller cells in rd10; Myd88-/- mice.
CONCLUSIONS: Myd88 deficiency accelerates retinal degeneration in rd10 mice, accompanied by an earlier onset of microglial infiltration and altered glia-related gene expression.
METHODS: Rd10 mice were crossed with Myd88-/- mice to produce rd10; Myd88-/- mice. The retinal phenotype was assessed by TUNEL, hematoxylin and eosin (H&E) staining, and electroretinography. Retinal microglia were immunostained with Iba-1. Retinal mRNA profiles associated with neuroinflammation were analyzed using a NanoString Neuroinflammation panel.
RESULTS: Myd88 deficiency increased the number of TUNEL-positive cells in the outer nuclear layer (ONL) and exacerbated ONL thinning at postnatal day 18 and 21 (P < 0.01, each). Consistent with these findings, the scotopic electroretinogram (ERG) showed lower b-wave amplitudes in rd10; Myd88-/- mice compared with rd10 mice (P < 0.01). Microglial infiltration into the outer retina showed an early but transient increase at P18, followed by a reduction at P21 in rd10; Myd88-/- mice. Retinal mRNA profiling revealed increased expression of Ifitm3 and Serpina3n, markers of astrocytic glia, in rd10; Myd88-/- mice. Immunostaining confirmed the upregulation of IFITM3 and SERPINA3N in astrocytes and Müller cells in rd10; Myd88-/- mice.
CONCLUSIONS: Myd88 deficiency accelerates retinal degeneration in rd10 mice, accompanied by an earlier onset of microglial infiltration and altered glia-related gene expression.