Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration

Purpose. To determine the pathogenesis of an autosomal dominant late-onset retinal degeneration by studies of the retinal histopathology, phenotype of family members, and candidate genes for the disease. Methods. The retina from an 80-year-old patient donor was prepared for light and electron microscopy, including special stains and immunocytochemistry. Family members were examined clinically and with retinal function tests. Rhodopsin, peripherin//?DS, and TIMP3 genes were screened for mutations, and linkage analysis was performed with short tandem repeat polymorphisms flanking these genes. Results. Affected family members had nyctalopia in the sixth decade of life and severe visual loss developed by the eighth decade. The donor retina showed marked loss of photoreceptors except in the inferior periphery. A thick layer of extracellular deposits was present between the RPE and Bruch's membrane in all retinal regions. A 70-year-old affected family member had a retinopathy resembling retinitis pigmentosa. Her 42-year-old daughter had a patch of punctate yellow-white lesions in one fundus and abnormal dark adaptation. The 50-year-old son of the donor had normal fundi but abnormal dark adaptation and electroretinography. No mutations were detected in the coding sequence of the rhodopsin, peripherin/ilDS, and TIMP3 genes. Rhodopsin and TIMP3 were further excluded with linkage analysis. Conclusions. This novel retinal degeneration shares histopathologic and clinical features with both Sorsby fundus dystrophy and retinitis pigmentosa. The sub-RPE deposits may disrupt the exchange of nutrients and metabolites between the retina and the choriocapillaris, leading to photoreceptor dysfunction and degeneration. Invest Ophthalmol Vis Sci. 1996; 37:1772-1782 .LJeposits between the retinal pigment epithelium (RPE) and Bruch's membrane are characteristic of age-related macular degeneration (ARMD) 1 and Sorsby fundus dystrophy (SFD) . 2 It has been hypothesized 3 A that such sub-RPE deposits may disrupt transport processes between the choriocapillaris and photoreceptors and lead to loss of vision. We obtained the eyes of a patient donor from

Rod photoreceptor differentiation in fetal and infant human retina

Human rods and cones are arranged in a precise spatial mosaic that is critical for optimal functioning of the visual system. However, the molecular processes that underpin specification of cell types within the mosaic are poorly understood. The progressive differentiation of human rods was tracked from fetal week (Fwk) 9 to postnatal (P) 8 months using immunocytochemical markers of key molecules that represent rod progression from post-mitotic precursors to outer segment-bearing functional photoreceptors. We find two phases associated with rod differentiation. The early phase begins in rods on the foveal edge at Fwk 10.5 when rods are first identified, and the rod-specific proteins NRL and NR2e3 are detected. By Fwk 11-12, these rods label for interphotoreceptor retinoid binding protein, recoverin, and aryl hydrocarbon receptor interacting protein-like 1. The second phase occurs over the next month with the appearance of rod opsin at Fwk 15, closely followed by the outer segment proteins rod GTP-gated sodium channel, rod arrestin, and peripherin. TULP is expressed relatively late at Fwk 18-20 in rods. Each phase proceeds across the retina in a central-peripheral order, such that rods in far peripheral retina are only entering the early phase at the same time that cells in central retina are entering their late phase. During the second half of gestation rods undergo an intracellular reorganization of these proteins, and cellular and OS elongation which continues into infancy. The progression of rod development shown here provides insight into the possible mechanisms underlying human retinal visual dysfunction when there are mutations affecting key rod-related molecules

The Role of Spirituality in Conceptualizations of Health Maintenance and Healthy Aging Among Latin American Immigrants.

ObjectivesWe aimed to investigate ways in which spirituality was conceptualized in relationship to maintaining brain health and healthy aging in a cohort of older adults who immigrated to the United States from diverse regions of Latin America, in order to ultimately develop culturally-tailored brain health promotion approaches.DesignWe conducted a qualitative study using semi-structured interviews.SettingParticipants were recruited from community centers and by a memory care center at a large academic medical center.ParticipantsWe interviewed 30 Spanish-speaking immigrants over age 60. Questions addressed perspectives about the brain, aging, and dementia. Interviews were coded for themes.MeasurementsThematic analysis was used to analyze participants' responses.ResultsWe identified 5 themes: (1) expressing gratitude to God for mental and physical health, (2) putting the onus of life and death in God's hands, (3) using church as a place to socialize and build community as an approach to leading a healthy lifestyle, (4) using prayer as nourishment for the soul and the brain, and (5) gaining inner-peace and calm, and thus maintaining a healthy life, due to a connection with God.ConclusionThe incorporation of customized spiritual interventions may be a mechanism by which to increase the effectiveness of brain health promotion efforts

Perceptions of and Knowledge Acquisition about Brain Health and Aging among Latin American Immigrants:A QualitativePaper

ObjectivesOlder immigrants of Latin American descent are disproportionately impacted by dementia, yet little is known about their dementia- and brain health-related knowledge. We explored perspectives on brain health and aging in this population to inform the development of culturally-relevant interventions.MethodsIndividual, semi-structured interviews were conducted with 30 Spanish-speaking immigrants over 60. Questions addressed knowledge about the brain, perceptions of healthy and unhealthy aging, ideas of how to take care of one's brain, and where knowledge was acquired. Responses were analyzed using thematic analysis.ResultsThe following themes emerged: (1) Descriptions of the brain varied, from anatomy, cognition, and psychology to disease. (2) Perceptions of healthy aging included independence, memory, emotions, and orientation. (3) Ideas of how to care for the brain included physical, social, and cognitive engagement. (4) Knowledge was acquired in childhood, communities, healthcare settings, careers, and media.ConclusionsResults showed significant variability in knowledge. Findings may be leveraged to improve interventions that address brain health literacy disparities among older Latin American immigrants.Clinical implicationsTakeaways involve increasing education about the structure and functions of the brain, promoting realistic understandings of what nonnormative brain aging entails, and increasing knowledge of empirically-supported maintenance approaches. Dissemination may be increased via healthcare providers, community centers, churches, and media