Abstract:
Purpose:Aging is a critical risk factor for the development of retinal diseases, but how aging perturbs ocular homeostasis and contributes to disease is unknown. We identified transmembrane protein 135 (Tmem135) as a gene important for regulating retinal aging and mitochondrial dynamics in mice. Overexpression of Tmem135 causes mitochondrial fragmentation and pathologies in the hearts of mice. In this study, we examine the eyes of mice overexpressing wild-type Tmem135 (Tmem135 TG) and compare their phenotype to Tmem135 mutant mice. Methods:Eyes were collected for histology, immunohistochemistry, electron microscopy, quantitative PCR, and Western blot analysis. Before tissue collection, electroretinography (ERG) was performed to assess visual function. Mouse retinal pigmented epithelium (RPE) cultures were established to visualize mitochondria. Results:Pathologies were observed only in the RPE of Tmem135 TG mice, including degeneration, migratory cells, vacuolization, dysmorphogenesis, cell enlargement, and basal laminar deposit formation despite similar augmented levels of Tmem135 in the eyecup (RPE/choroid/sclera) and neural retina. We observed reduced mitochondria number and size in the Tmem135 TG RPE. ERG amplitudes were decreased in 365-day-old mice overexpressing Tmem135 that correlated with reduced expression of RPE cell markers. In Tmem135 mutant mice, RPE cells are thicker, smaller, and denser than their littermate controls without any signs of degeneration. Conclusions:Overexpression and mutation of Tmem135 cause contrasting RPE abnormalities in mice that correlate with changes in mitochondrial shape and size (overfragmented in TG vs. overfused in mutant). We conclude proper regulation of mitochondrial homeostasis by TMEM135 is critical for RPE health.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Landowski M,Grindel S,Shahi PK,Johnson A,Western D,Race A,Shi F,Benson J,Gao M,Santoirre E,Lee WH,Ikeda S,Pattnaik BR,Ikeda Adoi
10.1167/iovs.61.12.16subject
Has Abstractpub_date
2020-10-01 00:00:00pages
16issue
12eissn
0146-0404issn
1552-5783pii
2770927journal_volume
61pub_type
杂志文章abstract:PURPOSE:To determine whether caspase or cathepsin pathways are activated in human retinal pigment epithelial cells (ARPE-19) after exposure to 7-ketocholesterol (7kCh). METHODS:ARPE-19 cells were exposed to 7kCh with or without z-VAD-fmk, a pan-caspase inhibitor. Caspase-3, -8, and -9 activities were measured by a flu...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0333
更新日期:2006-12-01 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:Strabismic amblyopia is typically associated with several visual deficits, including loss of contrast sensitivity in the amblyopic eye and abnormal binocular vision. Binocular summation ratios (BSRs) are usually assessed by comparing contrast sensitivity for binocular stimuli (sens(BIN)) with that measured in t...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0194
更新日期:2007-11-01 00:00:00
abstract:PURPOSE:To investigate the effects of reducing connexin (Cx) diversity in the lens when the amount of connexin protein is nearly constant. METHODS:Lenses in which the Cx50 coding region was replaced by that of Cx46 (knockin [KI]), were compared with wild type (WT) and Cx50-knockout (KO) lenses. Gap junctional conducta...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0445
更新日期:2004-10-01 00:00:00
abstract:Purpose:Adult central nervous system (CNS) neurons are unable to regenerate their axons after injury. Krüppel-like transcription factor (KLF) family members regulate intrinsic axon growth ability in vitro and in vivo, but mechanisms downstream of these transcription factors are not known. Methods:Purified retinal gang...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23319
更新日期:2018-06-01 00:00:00
abstract:Purpose:To identify the role of the BBSome protein Bardet-Biedl syndrome 5 (BBS5) in photoreceptor function, protein trafficking, and structure using a congenital mutant mouse model. Methods:Bbs5-/- mice (2 and 9 months old) were used to assess retinal function and morphology. Hematoxylin and eosin staining of retinal...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.10.17
更新日期:2020-08-03 00:00:00
abstract::Bovine rod outer segments (ROS) specifically stimulate DNA synthesis in lymphocyte cultures from guinea pigs preimmunized with ROS. At doses above 10 microgram/ml protein, however, preparations of ROS inhibit DNA and RNA synthesis by the sensitized lymphocytes or by normal lymphocytes reacting to mitogens. The inhibti...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract:PURPOSE:Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and, therefore, it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association, and genetic functional assay to evaluate FGF10 gene for myopia. METHODS:The expre...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-11814
更新日期:2013-05-07 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:In patients diagnosed with Best vitelliform macular dystrophy (BVMD), quantitative fundus autofluorescence (qAF), near-infrared fundus autofluorescence (NIR-AF), and spectral-domain optical coherence tomography (SD-OCT) were used to elucidate pathogenic mechanisms. Methods:Fourteen patients heterozygous for BE...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.19-26571
更新日期:2019-05-01 00:00:00
abstract:PURPOSE:To investigate the role of intralysosomal redox-active iron in oxidative stress-induced damage in trabecular meshwork (TM) cells. METHODS:Chronic oxidative stress was applied using the hyperoxic model; acute oxidative stress was applied with H(2)O(2). Microarray analysis was performed using microarrays. mRNA a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5410
更新日期:2010-12-01 00:00:00
abstract:PURPOSE:In MRL/Mp-lpr/lpr (MRL/lpr) and MRL/Mp-+/+ (MRL/+) mice, a T-cell-driven lacrimal gland inflammation spontaneously develops that is a model for Sjögren's syndrome. The lacrimal gland lesions in these mice were evaluated by immunohistochemistry for the relative contributions of T-helper (Th)1 versus Th2 immune r...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::This study used primary cultures of conjunctival and corneal epithelial cells from rabbit, monkey and humans to investigate the infection process and host interactions of chlamydia. The epithelial cells were isolated from bulbar and palpebral conjunctivae and the cornea following incubation with EDTA or dispase and mi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::Topical application of Prostaglandin F2 alpha (PGF2 alpha) to the eye reduces intraocular pressure (IOP) in all mammalian species studied thus far, including humans. The L-isopropylester derivative is currently the one most commonly used in experimental and clinical studies. Dose-response relationships were determined...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract:PURPOSE:To examine the possible presence of a major gene determining susceptibility to cortical cataract. METHODS:The percentage of the lens area involved with cortical opacity, summed over both eyes, was evaluated in 1275 individuals from the Beaver Dam Eye Study. After adjusting for the effects of age and sex, these...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To test the hypothesis that retinal hypoxia is present during vascular development in normal rat pups and in a newborn rat model of retinopathy of prematurity (ROP). METHODS:Preretinal vitreous PO(2) measurements were made during room air breathing using (19)F magnetic resonance spectroscopy (MRS) and a perflu...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-1122
更新日期:2003-07-01 00:00:00
abstract::Critical flicker frequency (CFF) was measured for stimuli varying in chromaticity only and in luminance only for patients with multiple sclerosis (MS) and for matched normal controls. The two CFF measurements showed different underlying linear interdependencies for the two groups, consistent with a greater loss of tem...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract:PURPOSE:To study the relationships between the refractive power of the crystalline lens, overall refractive error of the eye, and degree of nuclear cataract. METHODS:All phakic participants of the population-based Central India Eye and Medical Study with an age of 50+ years were included. Calculation of the refractive...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.11-8523
更新日期:2012-02-01 00:00:00
abstract:PURPOSE:To study the oxygen-saturation profiles in RP and macular dystrophies and compare them with age-matched healthy controls. METHODS:In a cross-sectional prospective study, 62 subjects with RP, 23 with macular dystrophies, and 78 controls were enrolled, and retinal oximetry was performed with the Oxymap T1 retina...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15993
更新日期:2015-05-01 00:00:00
abstract::In vivo conjunctival epithelial healing in albino rabbits was investigated by light microscopy following both n-heptanol and trephined conjunctival wounding. Reepithelialization occurred faster following n-heptanol treatment (3 days) versus trephination (6-7 days). No goblet cells were present in the migrating epithel...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::Previous studies have shown that aqueous humor of calf and human eyes contains about 25 microM hydrogen peroxide. We have studied the removal of hydrogen peroxide by the outflow pathway of intact, freshly enucleated, calf eyes. Eyes were immersed under silicone oil that had a density greater than water and medium cont...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract:Purpose:To enumerate the ocular surface fungal microbiome of healthy human eyes by using next-generation sequencing (NGS). Methods:Tarsal and fornix conjunctiva from the lower and upper lids of both eyes of healthy individuals were swabbed in duplicate separately. A total of 34 samples were collected from both the eye...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-26076
更新日期:2019-01-02 00:00:00
abstract::We have investigated suprathreshold contrast sensitivity and binocular interactions in strabismic and anisometropic amblyopes using a reaction time paradigm. For every spatial frequency, reaction time increased as the grating contrast decreased. At all spatial frequencies and contrast values the reaction times using t...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract:PURPOSE:To determine whether adenovirus vectors are capable of transferring a foreign active protein to the perfused anterior segment of the human eye. METHODS:Primary cultures from the human trabecular meshwork tissue were exposed to replication-deficient adenovirus Av1LacZ4 carrying the reporter beta-galactosidase g...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::Retinal dysplasia is a failure in normal retinal development. The morphologic sequence of the dysplastic processes was examined in fetuses and neonates from dogs affected with an inherited form of retinal dysplasia. The dysplastic change has its onset at 45-50 days' gestation and is most prominent in the dorsal peripa...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract:PURPOSE:Videokeratography is a powerful tool for the diagnosis of corneal shape abnormalities. However, interpretation of the topographic map is sometimes difficult, especially when pathologies with similar topographic patterns are suspected. The neural networks model, an artificial intelligence approach, was applied f...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract:PURPOSE:To link psychophysical thresholds for blind spot awareness and filling-in with early neural components that underpin these perceptions. METHODS:Blind spot dimensions were quantified, after which an intrinsic stimulus (i.e., a rectangular bar of varying length centered within the blind spot) was used to determi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5910
更新日期:2011-01-25 00:00:00
abstract:PURPOSE:To examine changes in spherical equivalent over a 5-year period in persons 43 to 84 years of age. METHODS:All people 43 to 84 years of age and living in Beaver Dam, Wisconsin, in 1988 were invited for a baseline examination (1988-1990) and a 5-year follow-up examination (1993-1995). Refractions were determined...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract:PURPOSE:Acute optic neuritis (ON) is often followed by recovery of visual function. Although this recovery is mainly attributable to resolution of the acute inflammation, the redistribution of ion channels along the demyelinated membrane, and subsequent remyelination, part of it may be the result of neural plasticity. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4577
更新日期:2010-05-01 00:00:00
abstract::We studied the effect of topical timolol maleate 0.5% on the retinal circulation of eyes with ocular hypertension using laser Doppler velocimetry and monochromatic fundus photography. Patients with ocular hypertension had normal eye examinations and had documented elevated intraocular pressures of 23 mmHg or higher on...
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:1990-03-01 00:00:00