Oral 8-aminoguanine against age-related retinal degeneration.

Visual decline in the elderly is often attributed to retinal aging, which predisposes the tissue to pathologies such as age-related macular degeneration. Currently, effective oral pharmacological interventions for retinal degeneration are limited. We present a novel oral intervention, 8-aminoguanine (8-AG), targeting age-related retinal degeneration, utilizing the aged Fischer 344 rat model. A low-dose 8-AG regimen (5 mg/kg body weight) via drinking water, beginning at 22 months for 8 weeks, demonstrated significant retinal preservation. This was evidenced by increased retinal thickness, improved photoreceptor integrity, and enhanced electroretinogram responses. 8-AG effectively reduced apoptosis, oxidative damage, and microglial/macrophage activation associated with aging retinae. Age-induced alterations in the retinal purine metabolome, characterized by elevated levels of inosine, hypoxanthine, and xanthine, were partially mitigated by 8-AG. Transcriptomics highlighted 8-AG's anti-inflammatory effects on innate and adaptive immune responses. Extended treatment to 17 weeks further amplified the retinal protective effects. Moreover, 8-AG showed temporary protective effects in the RhoP23H/+ mouse model of retinitis pigmentosa, reducing active microglia/macrophages. Our study positions 8-AG as a promising oral agent against retinal aging. Coupled with previous findings in diverse disease models, 8-AG emerges as a promising anti-aging compound with the capability to reverse common aging hallmarks.

Compensation of inner retina to early-stage photoreceptor degeneration in a RhoP23H/+ mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal disorder characterized by the degeneration of photoreceptors. RhoP23H/+ mice, which carry a Pro23His mutation in the RHODOPSIN (Rho) gene, are one of the most studied animal models for RP. However, except for the photoreceptors, other retinal neural cells have not been fully investigated in this model. Here, we record the temporal changes of the retina by optical coherence tomography (OCT) imaging of the RhoP23H/+ mice, from early to mid-phase of retinal degeneration. Based on thickness analysis, we identified a natural retinal thickness adaption in wild-type mice during early adulthood and observed morphological compensation of the inner retina layer to photoreceptor degeneration in the RhoP23H/+ mice, primarily on the inner nuclear layer (INL). RhoP23H/+ mice findings were further validated via: histology showing the negative correlation of INL and ONL thicknesses; as well as electroretinogram (ERG) showing an increased b-wave to a-wave ratio. These results unravel the sequential morphologic events in this model and suggest a better understanding of retinal degeneration of RP for future studies.

Characteristics associated with barriers to eye care: A cross-sectional survey at a free vision screening event.

INTRODUCTION: Social determinants of health can limit access to regular eye care, but their role in ophthalmology is underexamined. The purpose of this study is to assess the relationship between patient characteristics and self-reported barriers to eye care. METHODS: This anonymous, cross-sectional survey was conducted at a two-day free eye clinic event in Pittsburgh, Pennsylvania. Adult patients presenting for vision screening were eligible to participate. Patient characteristics (demographics, health status) and self-reported barriers to eye care were collected. Predictors of barriers to eye care were analyzed using binary logistic regression. RESULTS: Of 269 eligible, consecutive patients approached for survey completion, 183 comprised the volunteer sample. The 183 participants (105 female patients [59%]) had a mean (standard deviation) age of 53 (15) years, and generally self-identified as Black (74, 46%) or White (67, 41%). While a third reported having no health insurance (60, 34%), the remaining two-thirds of participants had public (84, 48%) or private coverage (34, 19%). Three-quarters of respondents reported at least one barrier to receiving regular eye care (136, 76%), most commonly medical costs (89, 50%) and insurance issues (73, 41%). Not having health insurance or vision insurance was strongly associated with reporting at least one barrier to care (OR 5.00, p=0.002, and OR 7.46, p<0.001, respectively). Those with self-reported eye disease were more likely to report transportation difficulties (OR 4.45, p=0.013), and employed participants reported difficulty getting time off work to attend eye exams (OR 7.73, p=0.002). Finally, compared to Black race, White race was associated with a higher likelihood of reporting any barrier to care (OR 2.79, p=0.013). CONCLUSION: Three-quarters of vision screening attendees reported at least one barrier to regular eye care, most commonly medical costs and insurance.

Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa.

Rhodopsin-associated (RHO-associated) retinitis pigmentosa (RP) is a progressive retinal disease that currently has no cure. RHO protein misfolding leads to disturbed proteostasis and the death of rod photoreceptors, resulting in decreased vision. We previously identified nonretinoid chaperones of RHO, including YC-001 and F5257-0462, by small-molecule high-throughput screening. Here, we profile the chaperone activities of these molecules toward the cell-surface level of 27 RP-causing human RHO mutants in NIH3T3 cells. Furthermore, using retinal explant culture, we show that YC-001 improves retinal proteostasis by supporting RHO homeostasis in RhoP23H/+ mouse retinae, which results in thicker outer nuclear layers (ONL), indicating delayed photoreceptor degeneration. Interestingly, YC-001 ameliorated retinal immune responses and reduced the number of microglia/macrophages in the RhoP23H/+ retinal explants. Similarly, F5257-0462 also protects photoreceptors in RhoP23H/+ retinal explants. In vivo, intravitreal injection of YC-001 or F5257-0462 microparticles in PBS shows that F5257-0462 has a higher efficacy in preserving photoreceptor function and delaying photoreceptor death in RhoP23H/+ mice. Collectively, we provide proof of principle that nonretinoid chaperones are promising drug candidates in treating RHO-associated RP.

A Required Ophthalmology Rotation: Providing Medical Students with a Foundation in Eye-Related Diagnoses and Management.

Introduction: Current ophthalmologic training in medical school is inadequate in preparing medical students to handle basic eye complaints as nonophthalmology residents. Most medical students are uncomfortable performing eye examinations, but increased ophthalmology training improves confidence in this area. The University of Pittsburgh School of Medicine (UPSOM) teaches students the basics of ophthalmology with a required 1-week rotation during the 1-month specialty care clerkship (SCC), providing students with skills to perform rudimentary eye examinations as nonophthalmology providers. Methods: Within a 1-week ophthalmology rotation, we developed a series of interactive case-based teaching sessions, handouts, and homework that accompanied clinical instruction to familiarize third- and fourth-year medical students with ophthalmic equipment, terminology, diagnosis, and management. Of learners, 67 (roughly 11 per cohort) rotated on six consecutive SCCs beginning in May 2019. All learners completed an in-house exam and received resident clinical evaluations at the end of their rotation. Results: Of the 64 participants who responded to the survey, 100% rated the quality of teaching sessions outstanding or good, and 83% of students strongly agreed or agreed with the statement, "I believe the overall teaching in the ophthalmology clinical settings was good quality." The average clinical and exam score for ophthalmology over 6 months was 4.5 out of 5, and 83% respectively. Discussion: Generally positive student feedback as well as high clinical and exam scores suggested that the required UPSOM ophthalmology clerkship was both engaging and effective. This course can be easily adapted to teach students at other medical institutions.