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Immunol."],"abstract":"<jats:p>The axons of retinal ganglion cells (RGCs) pass through the optic nerve head (ONH) and form the optic nerve (ON). The ONH serves as an anatomical interface between the vitreous cavity and subarachnoid space. After inducing acute neuroinflammation by intravitreal injection of lipopolysaccharides (LPS), we observed inflammatory activation in the retina, but detect no signs of inflammation in the posterior ON or infiltration of inflammatory cells in the ONH. Therefore, we hypothesized that the ONH functions as a barrier to vitreous inflammation. Using transmission electron microscopy, we identified significant increase in G-ratio in the posterior ON on day 7 post intravitreal injection (PII) of LPS compared with the phosphate buffered saline (PBS) group. Moreover, using confocal imaging of <jats:italic>ex vivo<\/jats:italic> tissue extracted from <jats:italic>Aldh1L<\/jats:italic>1-eGFP reporter mice, we observed that the ONH astrocytes altered their spatial orientation by elongating their morphology along the axonal axis of RGCs in LPS- versus PBS-treated eyes; this was quantified by the ratio of longitudinal (D<jats:sub>L<\/jats:sub>) and transverse (D<jats:sub>T<\/jats:sub>) diameter of astrocytes and the proportion of longitudinally locating astrocytes. Supportive evidences were further provided by transmission electron microscopic imaging in rat ONH. We further conducted RNA sequencing of ONH on day 1 PII and found LPS induced clear upregulation of immune and inflammatory pathways. Furthermore, gene set enrichment analysis revealed that astrocyte and microglia contributed prominently to the transcriptomic alterations in ONH. Here, we report that the vitreous infectious insults induce morphological changes of ONH astrocytes and transcriptomic alterations in the ONH. Glial responses in the ONH may defend against vitreous infectious insults and serve as a barrier to inflammation for the central nervous system.<\/jats:p>","DOI":"10.3389\/fimmu.2022.987771","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T10:03:48Z","timestamp":1663668228000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Optic nerve head: A gatekeeper for vitreous infectious insults?"],"prefix":"10.3389","volume":"13","author":[{"given":"Wenwen","family":"Lai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangyi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saiyue","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gezhi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengfei","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.800998","article-title":"The evolution of orbital implants and current breakthroughs in material design, selection, characterization, and clinical use","volume":"9","author":"Chen","year":"2021","journal-title":"Front Bioeng Biotechnol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.clae.2021.02.007","article-title":"CLEAR - contact lens technologies of the future","volume":"44","author":"Jones","year":"2021","journal-title":"Cont Lens Anterior Eye."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000002670","article-title":"Fungal necrotizing scleritis after intravitreal injection therapy","volume":"40","author":"Hern\u00e1ndez-Pons","year":"2021","journal-title":"Cornea."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202156","article-title":"Intravitreal pro-inflammatory cytokines in non-obese diabetic mice: Modelling signs of diabetic retinopathy","volume":"13","author":"Mugisho","year":"2018","journal-title":"PloS One"},{"key":"B5","article-title":"EIU in the rat promotes the potential of syngeneic retinal cells injected into the vitreous cavity to induce PVR","volume":"41","author":"Behar-Cohen","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-018-1727-5","article-title":"Connexin43 hemichannel block protects against the development of diabetic retinopathy signs in a mouse model of the disease","volume":"97","author":"Mugisho","year":"2019","journal-title":"J Mol Med (Berl)."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpet.2020.12.003","article-title":"Preclinical evaluation of TSPO and MAO-b PET radiotracers in an LPS model of neuroinflammation","volume":"16","author":"Narayanaswami","year":"2021","journal-title":"PET Clin"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511003112","article-title":"Imaging robust microglial activation after lipopolysaccharide administration in humans with PET","volume":"112","author":"Sandiego","year":"2015","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B9","article-title":"Endotoxin-induced uveitis in the rat","volume":"33","author":"Hoekzema","year":"1992","journal-title":"significance intraocular interleukin-6. 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