Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aging of skin is a continuous process that may be enhanced by sun exposure. Photoaging may provoke changes different from aging. Epidermal changes involve thinning of stratum spinosum and flattening of the dermo-epidermal junction. The senescent keratinocytes becomes resistant to apoptosis and may survive for a long time giving time for DNA and protein damage to accumulate with possible implication for carcinogenesis. The numbers of melanocytes decrease with age with dysregulation of melanocyte density resulting in freckles, guttate hypo-melanosis, lentigines and nevi. The number of dendritic Langerhans cells also decreases with age and the cells get less dendrites and have reduced antigen-trapping capacity. Aging involves dermal changes such as damage to elastic and collagen fibers giving thickened, tangled, and degraded non-functional fibers. Collagen intermolecular cross-links are stable and essential for stability and tensile strength. Cross-links increase with age converting divalent cross-links into mature trivalent cross-links of, e.g. histidinohydroxylysinonorleucine. Two mechanisms are involved; an enzyme-controlled process of maturation and a non-enzymatic glycosylation, the Maillard reaction leading to cross-links in proteins such as in collagen between arginine and lysine. Such may be seen with age and in diabetes mellitus. However, autofluorescence studies have shown that UVR reduces collagen cross-links. Natural photoprotection involves thickening of stratum corneum by sunlight and increased pigmentation. This leads to a factor 2 increase in photoprotection from spring until after-summer. The constitutive pigmentation is independent of age and thickness of stratum corneum is likewise independent of age. The minimal erythema dose is thus the same through life, when corrected for pigmentation or measured in areas with constitutive pigmentation.
 ...
PMID:Skin aging and natural photoprotection. 1503 73

The development of therapies for retinal disorders is hampered by a lack of appropriate animal models. Higher nonhuman primates are the only animals with retinal structure similar to humans, including the presence of a macula and fovea. However, few nonhuman primate models of genetic retinal disease are known. We identified a lineage of rhesus macaques with a frameshift mutation in exon 3 of the BBS7 gene c.160delG (p.Ala54fs) that is predicted to produce a non-functional protein. In humans, mutations in this and other BBS genes cause Bardet-Biedl syndrome, a ciliopathy and a syndromic form of retinitis pigmentosa generally occurring in conjunction with kidney dysfunction, polydactyly, obesity, and/or hypogonadism. Three full- or half-sibling monkeys homozygous for the BBS7 c.160delG variant, at ages 3.5, 4 and 6 years old, displayed a combination of severe photoreceptor degeneration and progressive kidney disease. In vivo retinal imaging revealed features of severe macular degeneration, including absence of photoreceptor layers, degeneration of the retinal pigment epithelium, and retinal vasculature atrophy. Electroretinography in the 3.5-year-old case demonstrated loss of scotopic and photopic a-waves and markedly reduced and delayed b-waves. Histological assessments in the 4- and 6-year-old cases confirmed profound loss of photoreceptors and inner retinal neurons across the posterior retina, with dramatic thinning and disorganization of all cell layers, abundant microglia, absent or displaced RPE cells, and significant gliosis in the subretinal space. Retinal structure, including presence of photoreceptors, was preserved only in the far periphery. Ultrasound imaging of the kidneys revealed deranged architecture, and renal histopathology identified distorted contours with depressed, fibrotic foci and firmly adhered renal capsules; renal failure occurred in the 6-year-old case. Magnetic resonance imaging obtained in one case revealed abnormally low total brain volume and unilateral ventricular enlargement. The one male had abnormally small testes at 4 years of age, but polydactyly and obesity were not observed. Thus, monkeys homozygous for the BBS7 c.160delG variant closely mirrored several key features of the human BBS syndrome. This finding represents the first identification of a naturally-occurring nonhuman primate model of BBS, and more broadly the first such model of retinitis pigmentosa and a ciliopathy with an associated genetic mutation. This important new preclinical model will provide the basis for better understanding of disease progression and for the testing of new therapeutic options, including gene and cell-based therapies, not only for BBS but also for multiple forms of photoreceptor degeneration.
 ...
PMID:Bardet-Biedl Syndrome in rhesus macaques: A nonhuman primate model of retinitis pigmentosa. 3158 38