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ArticleInternational ophthalmology2025

Intravitreal injection of SARM1 siRNA in TNF-induced optic nerve degeneration.

Yasushi Kitaoka, Chihiro Tsukahara, Naoki Fujita, Ibuki Arizono, Mizuki Otsubo, Kana Sase

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Article in International ophthalmology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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6 authors.

Yasushi KitaokaDepartment of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan. kitaoka@marianna-u.ac.jp.
Chihiro TsukaharaDepartment of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.
Naoki FujitaDepartment of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.
Ibuki ArizonoDepartment of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.
Mizuki OtsuboDepartment of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.
Kana SaseDepartment of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.

Funding

Grants-in-Aid from KAKENHI 23K15944Grants-in-Aid from KAKENHI 25K12899
6 · The paper itself

Abstract

purposeIntravitreal injections of some drugs such as anti-VEGF antibodies are available for certain human ocular diseases. Meanwhile, inhibition of SARM1 has been reported to exert neuroprotection in several neurodegenerative disease models. The aim of the current study is to investigate whether intravitreal injection of SARM1 siRNA can protect axons against TNF-induced optic nerve degeneration model.

methodsRats were received with intravitreal injection of PBS, TNF, TNF + SARM1 siRNA or SARM1 siRNA alone. Pre-injection of SARM1 siRNA + TNF and pre-injection of control siRNA + TNF groups were also made. Immunoblot analysis was carried out to evaluate SARM1 expression in the optic nerve. Morphometric analysis was carried out to evaluate the effects of SARM1 siRNA against axon loss induced by TNF. Immunohistochemical analysis was carried out to examine the localization of SARM1 in cross-sectioned optic nerves.

resultsImmunoblot analysis showed that intravitreal injection of SARM1 siRNA significantly decreased the SARM1 protein level in the optic nerve. Unexpectedly, axonal loss in the simultaneous intravitreal injection of SARM1 and TNF was almost the same as that in the TNF injection alone group. Pre-injection of SARM1 siRNA did not prevent axonal loss induced by TNF. There were no changes in SARM1 protein level in optic nerves 1 week after TNF injection compared with the PBS-injected group. Immunohistochemical analysis showed that the SARM1 immunoreactivity was colocalized with GFAP immunoreactivity in cross-sectioned optic nerves in both TNF and control groups.

conclusionThese results suggest that intravitreal injection of SARM1 siRNA may not prevent axonal degeneration induced by TNF.

Indexed as

Armadillo Domain ProteinsCytoskeletal ProteinsNerve DegenerationOptic NerveOptic Nerve DiseasesRNA, Small InterferingAnimalsAxonsDisease Models, AnimalImmunohistochemistryIntravitreal InjectionsMaleRatsRats, Sprague-DawleyTumor Necrosis Factor-alphaArmadillo Domain ProteinsCytoskeletal ProteinsRNA, Small InterferingTumor Necrosis Factor-alphaAxonOptic nerveSARM1TNF

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.