Mutations of the PRCD gene are associated with rod-cone degeneration in both dogs and humans. Prcd is expressed in the mouse eye as early as embryonic day 14. In the adult mouse retina PRCD is expressed in the outer segments of both rod and cone photoreceptors. Immunoelectron microscopy revealed that PRCD is located at the outer segment rim, and that it is highly concentrated at the base of the outer segment. Prcd-knockout mice present with progressive retinal degeneration, starting at 20 weeks of age and onwards. This process is reflected by a significant and progressive reduction of both scotopic and photopic electroretinographic responses, and by thinning of the retina, and specifically of the outer nuclear layer, indicating photoreceptor loss. Electron microscopy revealed severe damage to photoreceptor outer segments, which is associated with immigration of microglia cells to the Prcd-knockout retina, and accumulation of vesicles in the inter-photoreceptor space. Phagocytosis of photoreceptor outer segment discs by the retinal pigmented epithelium is severely reduced. Our data show that Prcd-knockout mice serve as a good model for retinal degeneration caused by PRCD mutations in humans. Our findings in these mice support the involvement of PRCD in outer segment disc formation of both rod and cone photoreceptors. Furthermore, they suggest a feedback mechanism which coordinates the rate of photoreceptor outer segment disc formation, shedding and phagocytosis. This study has important implications for understanding the function of PRCD in the retina, as well as for future development of treatment modalities for PRCD-deficiency in humans.

ObjectiveAbstracts submitted to meetings are subject to less rigorous peer review than full-text manuscripts. This study aimed to explore the publication outcome of abstracts presented at the American Academy of Ophthalmology (AAO) annual meeting.MethodsAbstracts presented at the 2008 AAO meeting were analyzed. Each presented abstract was sought via PubMed to identify if it had been published as a full-text manuscript. The publication outcome, journal impact factor (IF), and time to publication were recorded.ResultsA total of 690 abstracts were reviewed, of which 39.1% were subsequently published. They were published in journals with a median IF of 2.9 (range 0–7.2) and a median publication time of 426 days (range 0–2,133 days). A quarter were published in the journal Ophthalmology, with a shorter time to publication (median 282 vs. 534 days, p=0.003). Oral presentations were more likely to be published than poster presentations (57.8% vs. 35.9%, p<0.001) and in journals with higher IFs (3.2 vs. 2.8, p=0.02). Abstracts describing rare diseases had higher publication rates (49.4% vs. 38.0%, p=0.04) and were published in higher IF journals (3.7 vs. 2.9, p=0.03), within a shorter period of time (358 vs. 428 days, p=0.03). In multivariate analysis, affiliation with an institute located in the United States (p=0.002), abstracts describing rare diseases (p=0.03), and funded studies (p=0.03) were associated with publication in higher IF journals.ConclusionsAlmost 40% of abstracts were published. Factors that correlated with publication in journals with higher IF were a focus on rare diseases, affiliation with a US institute, and funding.

Inherited retinal diseases (IRDs) are heterogeneous phenotypes caused by variants in a large number of genes. Disease prevalence and the frequency of carriers in the general population have been estimated in only a few studies, but are largely unknown. To this end, we developed two parallel methods to calculate carrier frequency for mutations causing autosomal-recessive (AR) IRDs in the Israeli population. We created an SQL database containing information on 178 genes from gnomAD (including genotyping of 5706 Ashkenazi Jewish (AJ) individuals) and our cohort of >2000 families with IRDs. Carrier frequency for IRD variants and genes was calculated based on allele frequency values and the Hardy-Weinberg (HW) equation. We identified 399 IRD-causing variants in 111 genes in Israeli patients and AJ controls. For the AJ subpopulation, gnomAD and HW-based regression analysis showed high correlation, therefore allowing one to use HW-based data as a reliable estimate of carrier frequency. Overall, carrier frequency per subpopulation ranges from 1/2.2 to 1/9.6 individuals, with the highest value obtained for the Arab-Muslim subpopulation in Jerusalem reaching an extremely high carrier rate of 44.7%. Carrier frequency per gene ranges from 1/31 to 1/11994 individuals. We estimate the total carrier frequency for AR-IRD mutations in the Israeli population as over 30%, a relatively high carrier frequency with marked variability among subpopulations. Therefore, these data are highly important for more reliable genetic counseling and genetic screening. Our method can be adapted to study other populations, either based on allele frequency data or cohort of patients.