Search results for RPE

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Pathway (5 results from a total of 5)

Identifier: R-HSA-2466712
Species: Homo sapiens
Lipofuscin is a yellow-brown pigment grain composed mainly of lipids but also sugars and certain metals. Accumulation of lipofuscin is associated with degenerative diseases such as Alzheimer's disease, Parkinson's disease, chronic obstructive pulmonary disease and retinal macular degeneration.

A prominent component of lipofuscin in retinal pigment epithelial (RPE) cells is the bisretinoid A2E (di-retinoid-pyridinium-ethanolamine), the end-product of the condensation of 2 molecules of all-trans-retinal (atRAL) and phosphatidylethanolamine (PE) in photoreceptor outer disc membranes. Once formed, A2E is phagocytosed, together with outer segments (Kevany & Palczewski 2010), to RPE where it accumulates. There is no evidence as yet to indicate that A2E can be catabolised (Sparrow et al. 2012, Sparrow et al. 2010). A simplified biosynthetic pathway for A2E is described here.
Identifier: R-HSA-6809583
Species: Homo sapiens
Retinol binding protein (RBP4) delivers all-trans-retinol (atROL) from liver stores to peripheral tissues. Defects in RBP4 cause retinol-binding protein deficiency (RBP deficiency, MIM:180250), causing night vision problems and a typical 'xerophthalmic fundus' with progressive atrophy of the retinal pigment epithelium (RPE) (Seeliger et al. 1999, Biesalski et al. 1999).
Identifier: R-HSA-2453902
Species: Homo sapiens
The retinoid cycle (also referred to as the visual cycle) is the process by which the visual chromophore 11-cis-retinal (11cRAL) is released from light-activated opsins in the form all-trans-retinal and isomerized back to its 11-cis isomer ready for another photoisomerization reaction. This process involves oxidation, reduction and isomerization reactions and take place in the retinal pigment epithelium (RPE) and photoreceptor segments of the eye (von Lintig 2012, Blomhoff & Blomhoff 2006, von Lintig et al. 2010, D'Ambrosio et al. 2011). This section describes the retinoid cycle in rods during dark/twilight conditions.
Identifier: R-HSA-9730414
Species: Homo sapiens
Microphthalmia-associated transcription factor (MITF) is a key regulator of melanocyte differentiation and development during embryogenesis, of differentiation of melanocyte stem cells post-natally, and of melanoma cells.
Melanocytes are cells that possess specialized organelles called melanosomes that synthesize eumelanin and pheomelanin from tyrosine in a series of reactions. Melanosomes are transferred from cutaneous melanocytes to adjacent keratinocytes to provided protection against UV as well as coloration of skin, eye, hair, feathers and scales. Besides being found in the basal layer of the skin, melanocytes are also present in hair follicles, the inner ear and in the iris eye, among other places. The eye also contains a layer of melanosome-containing cells behind the retina, called the retinal pigment epithelium (RPE) (reviewed in Mort et al, 2015; D'Mello et al, 2016; Goding and Arnheiter, 2019; Le et al, 2021; Cui and Man, 2023).
Cutaneous melanocytes and their precursors, melanoblasts, arise during embryogenesis from neural crest cells that migrate dorsolaterally through the developing embryo (reviewed in Mort et al, 2015). They also arise from glial/melanoblast precursors migrating on a ventromedial pathway and along nerves (Adameyko et al, 2009). Expression of MITF is a key determinant of melanocyte fate, and mutations in MITF are associated with a variety of defects in pigmentation as well as with deafness (due to absence of melanocytes in teh inner ear) and microphthalmia (due to aberrant development of retina and RPE), among other conditions (reviewed in White and Zon, 2008; Mort et al, 2015; Goding and Arnheiter, 2019; Le et al, 2021).
The gene for MITF encodes several distinct isoforms based on alternative splicing. The gene has a 3' portion consisting of exons 2-9 that are generally shared by all transcripts. In mice and humans, the upstream region of the gene contains 9 exons, some of them coding, some not, and each regulated by its own promoter. Most of them are spliced to exon 2 via a common exon B. An exception is exon 1M which is directly spliced to exon 2, giving rise to the so-called M-isoform of MITF. This arrangement gives rise to a number of different mRNA and protein isoforms with preferential expression patterns. Exon 1A-containing transcripts, for instance, are ubiquitously expressed, exon 1H-containing transcripts are highly expressed in the heart, exon 1D-containing transcripts are expressed in the RPE, and exon 1M-containing transcripts are expressed in neural crest-derived melanocytes. Nevertheless, there is little information on whether the different isoforms have different functions except that exon 1B-containing transcripts (but not MITF-M) harbor a sequence subject to mTORC1 regulation (reviewed in Goding and Arnheiter, 2019; Vu et al, 2020). Most if not all transcripts come in two additional splice versions, one including and one excluding 18 bp of part of exon 6, called exon 6A, which encodes 6 amino acids lying upstream of the DNA-binding domain and which is regulated by MAPK signaling (Primot et al, 2010). They are usually referred to as the (+) and (-) versions of MITF. While the (-) version of a fragment of MITF-M has slightly reduced DNA-binding affinity compared to the (+) version, no specific role has so far been found for exon 6A (Pogenburg et al, 2012).(
This pathway focuses on the activity of the melanocyte lineage-specific transcription factor MITF-M, although some of the biology described may also be relevant for other MITF isoforms.
Identifier: R-HSA-2187335
Species: Homo sapiens
Rods and cones share the same mechanism for the phototransduction process but perform functionally different roles. Although cone photoreceptors make up around 5% of all photoreceptor cells and are outnumbered 20 to 1 by rod photoreceptors, they mediate daylight vision in the human eye whereas rods mediate twilight vision. Also, cones are around 100-times less light-sensitive than rods thereby depriving us of colour vision in dark conditions in which cones cannot function. Rod function saturates in even moderate amounts of light whereas cones can adjust to even very bright light conditions, a process called light adaptation. In bright conditions, rods can take up to one hour to regain their sensitivity whereas cones can recover in a few minutes, a process called dark adaptation and which allows us to retain visual perception in changing light conditions.

Cone cells express three types of opsin which allow colour discrimination. Long Wavelength Sensitive Opsin (OPN1LW) detects red , Short Wavelength Sensitive Opsin (OPN1SW) detects blue, and Medium Wavelength Sensitive Opsin (OPN1MW) detects green regions of the light spectrum.

In the canonical retinoid (visual) cycle, the visual chromophore is regenerated in reactions involving the rod outer segments (ROS) and the retinal pigment epithelium (RPE). For cones, chromophore recycling is independent of the RPE and instead involves Muller cells in the retina which supply the chromophore selectively to cones. The molecular steps of the cone retinoid (visual) cycle are outlined in this section. The ability of cones to react to bright and differing light conditions means it has to regenerate the chromophore much quicker than rods. All-trans-retinol (atROL) released from cone outer segments is taken up by Muller cells where it is directly isomerized back to 11-cis-retinol (11cROL) then esterified by LRAT. When required, these 11-cis-retinyl esters can be hydrolysed by 11-cis-RE hydrolases back to 11cROL then oxidised in the cone photoreceptor cell to regenerate 11-cis-retinal (11cRAL), the visual chromophore (see reviews von Lintig 2012, Wang & Kefalov 2011, Kefalov 2012, Wolf 2004).
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