Identification and characterization of rod-derived cone viability factor

Retinitis pigmentosa is an untreatable, inherited retinal disease that leads to blindness. The disease initiates with the loss of night vision due to rod photoreceptor degeneration, followed by irreversible, progressive loss of cone photoreceptor. Cone loss is responsible for the main visual handicap, as cones are essential for day and high-acuity vision. Their loss is indirect, as most genes associated with retinitis pigmentosa are not expressed by these cells. We previously showed that factors secreted from rods are essential for cone viability. Here we identified one such trophic factor by expression cloning and named it rod-derived cone viability factor (RdCVF). RdCVF is a truncated thioredoxin-like protein specifically expressed by photoreceptors. The identification of this protein offers new treatment possibilities for retinitis pigmentosa.     

An in vitro evaluation of novel NHA/zircon plasma coating on 316L stainless steel dental implant

The surface characteristics of an implant that influence the speed and strength of osseointegration include crystal structure and bioactivity. The aim of this study was to evaluate the bioactivity of a novel natural hydroxyapatite/zircon(NHA/zircon) nanobiocomposite coating on 316L stainless steel(SS) dental implants soaking in simulated body fluid. A novel NHA/zircon nanobiocomposite was fabricated with 0(control),5, 10, and 15 wt% of zircon in NHA using ball mill for 1 h. The composite mixture was coated on SS implants using a plasma spray method.Scanning electron microscopy(SEM) was used to evaluate surface morphology, and X-ray diffraction(XRD) was used to analyze phase composition and crystallinity(Xc). Further, calcium ion release was measured to evaluate the coated nanobiocomposite samples. The prepared NHA/zircon coating had a nanoscale morphological structure with a mean crystallite size of 30–40 nm in diameter and a bone-like composition,which is similar to that of the biological apatite of a bone. For the prepared NHA powder, high bioactivity was observed owing to the formation of apatite crystals on its surface. Both minimum crystallinity(Xc=41.1%) and maximum bioactivity occurred in the sample containing 10 wt% of zircon because of minimum Xcand maximum biodegradation of the coating sample.     

NMNAT1 mutations cause Leber congenital amaurosis

Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss. Two-thirds of LCA cases are caused by mutations in 17 known disease-associated genes (Retinal Information Network (RetNet)). Using exome sequencing we identified a homozygous missense mutation (c.25G>A, p.Val9Met) in NMNAT1 that is likely to be disease causing in two siblings of a consanguineous Pakistani kindred affected by LCA. This mutation segregated with disease in the kindred, including in three other children with LCA. NMNAT1 resides in the previously identified LCA9 locus and encodes the nuclear isoform of nicotinamide mononucleotide adenylyltransferase, a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD(+)) biosynthesis. Functional studies showed that the p.Val9Met alteration decreased NMNAT1 enzyme activity. Sequencing NMNAT1 in 284 unrelated families with LCA identified 14 rare mutations in 13 additional affected individuals. These results are the first to link an NMNAT isoform to disease in humans and indicate that NMNAT1 mutations cause LCA.     

Metabolic and redox signaling in the retina

Visual perception by photoreceptors relies on the interaction of incident photons from light with a derivative of vitamin A that is covalently linked to an opsin molecule located in a special subcellular structure, the photoreceptor outer segment. The photochemical reaction produced by the photon is optimal when the opsin molecule, a seven-transmembrane protein, is embedded in a lipid bilayer of optimal fluidity. This is achieved in vertebrate photoreceptors by a high proportion of lipids made with polyunsaturated fatty acids, which have the detrimental property of being oxidized and damaged by light. Photoreceptors cannot divide, but regenerate their outer segments. This is an enormous energetic challenge that explains why photoreceptors metabolize glucose through aerobic glycolysis, as cancer cells do. Uptaken glucose produces metabolites to renew that outer segment as well as reducing power through the pentose phosphate pathway to protect photoreceptors against oxidative damage.