Family History in the Primary Open-Angle African American Glaucoma Genetics Study Cohort.

PURPOSE: To determine the relationship between positive family history (FH) and primary open-angle glaucoma (POAG) diagnosis and clinical presentation in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) cohort. METHODS: FH of POAG in first-degree relatives was assessed in 2365 subjects in the POAAGG cohort. A standardized interview was used to assess FH of glaucoma, demographic characteristics, lifestyle choices, and medical and ocular comorbidities. RESULTS: Positive FH was associated with increased risk of POAG (age-adjusted odds ratio and 95% confidence interval 3.4 [2.8, 4.1]). In age-adjusted analysis among POAG cases, positive FH was associated with younger age (P < .001), female sex (P < .001), hypertension (P = .006), use of hypertension medication (P = .03), and prior glaucoma surgery (P = .02). Cases with positive FH also had thicker retinal nerve fiber layers (P = .03). CONCLUSIONS: The risk conferred by positive FH suggests strong genetic underpinnings for some patients with this disease, which will be investigated by genome-wide association studies and whole exome sequencing. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Immune challenges decrease biliverdin concentration in the spleen of northern Bobwhite quail, Colinus virginianus.

Most antioxidants have multiple functions; in addition to minimizing oxidative damage, many antioxidants have immune-modulating properties. For example, biliverdin is produced in the liver and spleen from the breakdown of heme, and has putative immune-suppressing and antioxidant properties. However, the majority of these properties have been investigated in vitro or in mammalian models, in which biliverdin reductase converts virtually all biliverdin to bilirubin. Thus, biliverdin's physiological roles remain largely untested. Here, we investigated whether biliverdin has immunomodulating roles by injecting Northern Bobwhite quail (Colinus virginianus) with either a vehicle control, lysed and rinsed pig red blood cells (pRBC) that contain erythrocyte antigens but no heme, or intact pRBC that contain both erythrocyte antigens and hemoglobin, thus increasing the amount of heme that can be converted to biliverdin. We then quantified hemagglutination and hemolysis ability, and biliverdin concentration in the liver and spleen, on 3, 6, and 9 days post-injection. We found that hemagglutination was greater in individuals that received intact pRBC, but not in those injected with heme-removed pRBC, demonstrating that biliverdin does not suppress immune function at this dosage. Biliverdin levels of liver and spleen were correlated within individuals, suggesting organism-level variation in biliverdin production. Lastly, individuals injected with intact pRBC had a reduced biliverdin concentration in the spleen, suggesting that immune challenges may reduce biliverdin production or accumulation. This initial investigation demonstrated that biliverdin may have more nuanced physiological roles than previously reported, supporting the value of further investigations into the physiology of biliverdin.

A missense mutation in ASRGL1 is involved in causing autosomal recessive retinal degeneration.

Inherited retinal dystrophies are a group of genetically heterogeneous conditions with broad phenotypic heterogeneity. We analyzed a large five-generation pedigree with early-onset recessive retinal degeneration to identify the causative mutation. Linkage analysis and homozygosity mapping combined with exome sequencing were carried out to map the disease locus and identify the p.G178R mutation in the asparaginase like-1 gene (ASRGL1), segregating with the retinal dystrophy phenotype in the study pedigree. ASRGL1 encodes an enzyme that catalyzes the hydrolysis of L-asparagine and isoaspartyl-peptides. Studies on the ASRGL1 expressed in Escherichia coli and transiently transfected mammalian cells indicated that the p.G178R mutation impairs the autocatalytic processing of this enzyme resulting in the loss of functional ASRGL1 and leaving the inactive precursor protein as a destabilized and aggregation-prone protein. A zebrafish model overexpressing the mutant hASRGL1 developed retinal abnormalities and loss of cone photoreceptors. Our studies suggest that the p.G178R mutation in ASRGL1 leads to photoreceptor degeneration resulting in progressive vision loss.

Carotenoid supplementation during adulthood, but not development, decreases testis size in mallards.

Nutritional constraints on reproduction are well-characterized in female animals, but rarely have particular nutrients been linked to male reproductive investments. Carotenoid pigments promote egg-laying and fertility in several animals, and are displayed externally within secondary sex traits by males of many colorful species to attract mates, but it is unclear if or how carotenoids affect male primary sex traits. We manipulated carotenoid availability in the diet of male mallards (Anas platyrhynchos) during both development and adulthood to determine effects on size and carotenoid content of the testes. We found that developmental carotenoid manipulations did not affect testis size or carotenoid concentration, but that increased carotenoid dietary levels at adulthood resulted in more carotenoid-rich, but smaller, testes. This latter result was surprising, given positive correlations in mammals between testicle size and carotenoid concentration. We also found negative correlations between testis size and carotenoid concentration for individual ducks, regardless of dietary treatment. These results suggest that carotenoid deposition into testis tissue can reduce investment in gonad size (and thus overall sperm count), although the functional consequences of this relationship remain to be tested.