Abstract:
Purpose:Single-cell RNA-sequencing (scRNA-seq) was used to interrogate the relatively rare stem (SC) and early transit amplifying (TA) cell populations in limbal/corneal epithelia from wild-type and autophagy-compromised mice. Methods:We conducted scRNA-seq on ocular anterior segmental tissue from wild-type and beclin 1-deficient (beclin1+/-) mice, using a 10X Gemomics pipeline. Cell populations were distinguished by t-distributed stochastic neighbor embedding. Seurat analysis was conducted to compare gene expression profiles between these two groups of mice. Differential protein expression patterns were validated by immunofluorescence staining and immunoblotting. Results:Unbiased clustering detected 10 distinct populations: three clusters of mesenchymal and seven clusters of epithelial cells, based on their unique molecular signatures. A discrete group of mesenchymal cells expressed genes associated with corneal stromal SCs. We identified three limbal/corneal epithelial cell subpopulations designated as stem/early TA, mature TA, and differentiated corneal epithelial cells. Thioredoxin-interacting protein and PDZ-binding kinase (PBK) were identified as novel regulators of stem/early TA cell quiescence. PBK arrested corneal epithelial cells in G2/M phase of the cell cycle. Beclin1+/- mice displayed a decrease in proliferation-associated (Ki67, Lrig1) and stress-response (H2ax) genes. The most increased gene in beclin1+/- mice was transcription factor ATF3, which negatively regulates limbal epithelial cell proliferation. Conclusions:Establishment of a comprehensive atlas of genes expressed by stromal and epithelial cells from limbus and cornea forms the foundation for unraveling regulatory networks among these distinct tissues. Similarly, scRNA-seq profiling of the anterior segmental epithelia from wild-type and autophagy-deficient mice provides new insights into how autophagy influences proliferation in these tissues.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Kaplan N,Wang J,Wray B,Patel P,Yang W,Peng H,Lavker RMdoi
10.1167/iovs.19-27656subject
Has Abstractpub_date
2019-08-01 00:00:00pages
3570-3583issue
10eissn
0146-0404issn
1552-5783pii
2748694journal_volume
60pub_type
杂志文章abstract:PURPOSE:Recent studies suggest that photoreceptor cells regulate local inflammation in the retina in diabetes. The purpose of this study was to determine if photoreceptor cells themselves produce inflammatory proteins in diabetes and if soluble factors released by photoreceptors in elevated glucose induce inflammatory ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19859
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:We showed previously that single nucleotide polymorphism (SNP) rs662702 in PAX6 may be located in a microRNA-328 binding site that causes susceptibility to high myopia. Our study was done to elucidate the role of PAX6 and its relationship with microRNA-328 in myopia. METHODS:A luciferase assay was used to conf...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-9272
更新日期:2012-05-31 00:00:00
abstract::Long-term S-antigen (S-Ag) specific T lymphocyte lines can induce experimental autoimmune uveoretinitis (EAU) when transferred into naive rats systemically or intravitreally. The uveitogenic lymphocyte line (ThS) stains positively for the ART 18 (IL-2 receptor) and W3/25 (T helper/inducer); negatively for OX6 (RT1B) a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract:PURPOSE:To examine the correlation between corneal acoustic impedance and Young's modulus in a canine eye model. METHODS:Twenty canine globes were recovered from healthy animals. Corneal acoustic impedance was measured in the intact globes using two methods: a quantitative ultrasound spectroscopy method and the reflec...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5723
更新日期:2011-02-09 00:00:00
abstract:PURPOSE:To evaluate the antilymphangiogenic potential of multi-target tyrosine kinase inhibitor sunitinib in corneal neovascularization (NV). METHODS:Inflammatory corneal NV was induced by thermal cauterization applied in the central cornea of mice, to which sunitinib malate was daily administered by gavage or not. At...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10856
更新日期:2013-05-03 00:00:00
abstract:PURPOSE:Tubby-like proteins (TULPs) are a family of four proteins, two of which have been linked to neurosensory disease phenotypes. TULP1 is a photoreceptor-specific protein that is mutated in retinitis pigmentosa, an inherited retinal disease characterized by the degeneration of rod and cone photoreceptor cells. To i...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0059
更新日期:2007-06-01 00:00:00
abstract:PURPOSE:To investigate the molecular mechanism of Rho-associated kinase (ROCK) inhibitors Y-27632 and Y-39983 on corneal endothelial cell (CEC) proliferation and their wound-healing effect. METHODS:The expression of G1 proteins of the cell cycle and expression of phosphorylated Akt in monkey CECs (MCECs) treated with ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12225
更新日期:2014-01-15 00:00:00
abstract:PURPOSE:In the rabbit iris sphincter muscle, sodium nitroprusside (SNP), a nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect tachykinergic contraction in vitro. The objectives of the current study were to clarify the mechanism for the different responsiveness to NO in cholinergic and tachyki...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract:Purpose:The purpose of this study was to evaluate the effect of gravity acceleration on choroidal and retinal nerve fiber layer (RNFL) thickness using swept-source optical coherence tomography (SS-OCT). Methods:Thirteen healthy volunteers who planned to participate in human centrifuge training as part of the flight su...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-21994
更新日期:2017-12-01 00:00:00
abstract:PURPOSE:To assess the impact of amblyopia, strabismus and glasses on subjective visual and psychological function among amblyopes. METHODS:Questionnaires were administered to 120 teenagers with amblyopia (cases), with residual amblyopia after treatment, or with or without strabismus and 120 control subjects (controls)...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1365
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:To examine immune processes in the lacrimal gland of patients with chronic graft-versus-host disease (cGVHD) by evaluating the expression of surface molecules associated with T-cell activation. METHODS:Antibodies to CD4, CD8, CD34, CD40, CD54, CD80, CD86, CD154, and HLA-DR were used for immunohistochemical ana...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-0699
更新日期:2003-05-01 00:00:00
abstract:PURPOSE:To evaluate the role of TIMP-1 in inherited retinal degeneration. METHODS:The genomic structure of the TIMP-1 gene was established and male patients with x-linked retinitis pigmentosa 2 from five families were screened for sequence alterations by direct sequencing in all exons, exon-intron boundaries, and the ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract:Purpose:The study aimed to provide a quantitative description of aqueous humor dynamics in healthy rat eyes. Methods:One eye of 26 anesthetized adult Brown-Norway rats was cannulated with a needle connected to a perfusion pump and pressure transducer. Pressure-flow data were measured in live and dead eyes by varying p...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-22915
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:The purpose of this study was to elucidate the differentiated expression patterns and phagocytic activities of two subtypes of microglia. METHODS:A rat optic nerve crush model was used to identify the expression patterns of two subtypes of microglia. Primary microglia were isolated from rat mixed glial culture...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18509
更新日期:2016-05-01 00:00:00
abstract:Purpose:Conventional full-field flash electroretinography (ERG) yields a single response waveform that can be useful in the early detection and diagnosis of many diseases affecting the retina. It is an objective measurement that probes the entire retina. However, localized areas of dysfunction have relatively small inf...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-20726
更新日期:2017-06-01 00:00:00
abstract:PURPOSE:To map the spatiotemporal decline in retinally driven activity in the superior colliculus (SC) of transgenic S334ter-line-3 rats that express a mutated rhodopsin, which causes photoreceptor degeneration. To determine whether transplantation of fetal retinal sheets into the subretinal space of these rats can rec...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-0615
更新日期:2003-04-01 00:00:00
abstract:PURPOSE:To learn whether locally expressed and systemic mediators might modulate the cholinergically induced transepithelial Cl(-) fluxes that underlie lacrimal fluid production. METHODS:Reconstituted epithelial monolayers were exposed to a submaximal dose of the muscarinic agonist, carbachol (CCh), or to one of sever...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10202
更新日期:2013-04-26 00:00:00
abstract:PURPOSE:Juvenile monkeys being trained on smooth-pursuit tasks exhibit ocular oscillations resembling pendular nystagmus. The purpose of this study was to analyze these oscillations, the effects of gabapentin on them, and responses of cerebellar floccular neurons to understand possible neuronal mechanisms. METHODS:Fou...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5903
更新日期:2011-06-01 00:00:00
abstract::Normal adult rabbit corneas were digested with 5% pepsin and their collagens extracted with acetic acid. Collagen extracts were fractionated by differential salt precipitation. The 2.5 M NaCl fraction was then redissolved with tris buffer and precipitated with sodium acetate. The precipitate contained a high-molecular...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract:PURPOSE:To determine whether vascular tone of isolated porcine retinal veins can be modulated by tissue-generated vasoactive factors such as endothelin-1 and adenosine. Such information may be useful in understanding the role of the retinal veins in regulating blood flow, and also provide a model for investigating new ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18358
更新日期:2016-02-01 00:00:00
abstract:PURPOSE:To test whether the incidence of long-term drift to timolol can be reduced by a "pulsatile" treatment (6 months timolol-2 months dipivefrin). METHODS:In a randomized clinical trial, 100 consecutive subjects with ocular hypertension or high-tension primary open-angle glaucoma in at least one eye were randomly a...
journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1996-03-01 00:00:00
abstract:PURPOSE:The fibrotic lens disorder posterior capsule opacification (PCO) develops in millions of patients following cataract surgery. PCO characteristics are extensive extracellular matrix (ECM) production and contraction of the posterior lens capsule, resulting in light-scattering ECM modification (wrinkling). The pro...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-9457
更新日期:2012-06-26 00:00:00
abstract:PURPOSE:To assess whether tonometric measurements of the drop in intraocular pressure (IOP) induced by 0.005% latanoprost are modified after photorefractive keratectomy (PRK). METHODS:Data from 24 randomly selected eyes of 24 patients (12 men and 12 women, mean age +/- SD: 31.7 +/- 6.2 years) who were undergoing bilat...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0625
更新日期:2004-03-01 00:00:00
abstract:PURPOSE:α-Crystallins are small heat shock proteins that regulate cellular damage and cell survival. Expression of the proteins of the crystallin superfamily in the retina and their role in neuronal cell survival were investigated in two animal models of diabetes and retinal neurons in culture. METHODS:Crystallin expr...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6931
更新日期:2011-08-24 00:00:00
abstract::Diabetes mellitus has been shown to be a factor in the development of corneal epithelial abnormalities in stressed human eyes, but the biochemical basis for this is not known. To see if sorbitol pathway activation might be involved, ocular surface epithelial healing rates and metabolites of the glycolytic and sorbitol...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1981-08-01 00:00:00
abstract:PURPOSE:To describe hereditary macular degeneration observed in the cynomolgus monkey (Macaca fascicularis), which shares phenotypic features with age-related macular degeneration in humans, and to test the involvement of candidate gene loci by mutation screening and linkage analysis. METHODS:Ophthalmic examinations w...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-1031
更新日期:2005-02-01 00:00:00
abstract:PURPOSE:To investigate corneal nerve damage and its subsequent regeneration after excimer laser photokeratectomy in rabbit eyes. METHODS:Corneal photokeratectomy was performed on the right eyes of 34 pigmented rabbits, while the left eyes were used as a control. A Summit UV 200 excimer laser (Summit Technology, Waltha...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract:Purpose:Basement membrane degradation and macrophage aggregation at the optic fissure margins are crucial to optic fissure closure during normal murine eye development. Basement membrane degradation is also an essential step in cancer development, and matrix metalloproteinases (MMPs) play an important role. In this stu...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-21841
更新日期:2018-03-01 00:00:00
abstract:PURPOSE:Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized mo...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6250
更新日期:2011-04-25 00:00:00
abstract:PURPOSE:Scleral proteoglycans were characterized from human donor eyes aged 2 months to 94 years to identify age-related changes in the synthesis and/or accumulation of these extracellular matrix components. METHODS:Newly synthesized proteoglycans (previously radiolabeled with 35SO4) and total accumulated scleral prot...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00