Search

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) characterized by atrophy of the retinal pigment epithelium (RPE), loss of photoreceptors, and disruption of choriocapillaris. Excessive light exposure is toxic to the retina and is a known risk factor for AMD. We first investigated the effects of blue light-induced phototoxicity on RPE and photoreceptors in nonhuman primates (NHPs, a model of progressive retinal degeneration) and then evaluated the potential cyto- and neuroprotective effects of the brimonidine drug delivery system (Brimo DDS). In the first set of experiments related to model development, parafoveal lesions of varying severity were induced using blue light irradiation of the retina of cynomolgus monkeys to evaluate the level of phototoxicity in the RPE and photoreceptors. RPE damage was assessed using fundus autofluorescence imaging to quantify areas of hypofluorescence, while thinning of the outer nuclear layer (ONL, photoreceptor nuclei) was quantified using optical coherence tomography (OCT). Photoreceptor function was assessed using multifocal electroretinography (mfERG). RPE damage progressively increased across all lesion severities from 2 to 12 weeks, as did the extent of ONL thinning. Lesions of high severity continued to show reduction in mfERG amplitude, reaching a statistically significant maximum reduction at 12 weeks. Collectively, the first set of experiments showed that blue light irradiation of the NHP eye resulted in progressive retinal degeneration identified by damage to RPE, ONL thinning, and disrupted photoreceptor function - hallmarks of GA in humans. We then used the model to evaluate the cyto- and neuroprotective effects of Brimo DDS, administered as a therapeutic after allowing the lesions to develop for 5 weeks. Placebo DDS or Brimo DDS were administered intravitreally and a set of untreated animals were used as an additional control. In the placebo DDS group, hypofluorescence area continued to increase from baseline, indicating progressive RPE damage, while progression was significantly slowed in eyes receiving Brimo DDS. Likewise, ONL thinning continued to progress over time in eyes that received the placebo DDS, but was reduced in Brimo DDS-treated eyes. Pharmacologically relevant brimonidine concentrations were sustained in the retina for up to 26 weeks following Brimo DDS administration. In summary, Brimo DDS demonstrated cyto- and neuroprotective effects in a novel NHP GA model of progressive retinal degeneration.

Sustainable transportation interventions affect public health in three ways: through ( a) reduced pollution emissions, ( b) increased physical activity, and ( c) reduced road accidents. The public health benefits that can be achieved through investment in sustainable transport thus are substantial. This study sought to estimate benefits from sustainable transport intervention in the city of Indore in the Indian state of Madhya Pradesh through the construction of a bus rapid transit (BRT) system along a main traffic corridor. The benefits were estimated with a health impact assessment methodology developed on the basis of modal shift and vehicle kilometers traveled. With the introduction of a BRT system, the study found that about 14 lives could be saved per year as a result of an increase in walking or cycling, a decrease in private vehicle use, and a reduction in air pollution exposure. Also, more than 96 deaths could be prevented from 2013 to 2017 along the BRT corridor when compared with current trends in motorization with no BRT system investment. The reduction in emissions between a business-as-usual scenario and post-BRT scenario was 11%. The mortality risk from exposure to particulate matter of up to 2.5 mm in size could be reduced by 1.1%. Even given the limitations with respect to the data and the assumptions made in the study, the results were significant enough to recommend that public health aspects be considered in the formulation of transport policy and in the maximization of benefits.

We investigated relations between macular retinal ganglion cell plus inner plexiform layer (RGC+IPL) thickness and macular retinal function revealed by multifocal electroretinonography (mfERG) in a nonhuman primate model of experimental glaucoma.Retinal ganglion cell (RGC) structure and function were followed with spectral-domain optical coherence tomography (SD-OCT) and ERGs in five macaques with unilateral experimental glaucoma. Linear regression was used to study correlations in control (Con) and experimental (Exp) eyes between peripapillary retinal nerve fiber layer (RNFL) thickness, macular RGC+IPL thickness, multifocal photopic negative response (mfPhNR) and high-frequency multifocal oscillatory potentials (mfOP) in slow-sequence mfERG, and low-frequency component (mfLFC) in global-flash mfERG. We used ANOVA and paired t-tests to compare glaucoma-related mfERG changes between superior and inferior hemifields, foveal hexagon, inner three rings, and four quadrants of macula.Average macular RGC+IPL and temporal RNFL thickness were strongly correlated (r(2) = 0.90, P0.001). In hexagon-by-hexagon analysis, all three mfERG measures were correlated (P0.001) with RGC+IPL thickness for Con (r(2), 0.33-0.51) and Exp eyes (r(2), 0.17-0.35). The RGC structural and functional metrics decreased as eccentricity increased. The reduction in amplitude of mfERG measures in Exp eyes relative to Con eyes was proportionally greater, in general, than the relative thinning of RGC+IPL at the same location for eyes in which structural loss was not evident, or mild to moderate. Although not statistically significant, percent amplitude reduction of mfERG measures was greatest in the inferior temporal quadrant.Macular RGC+IPL thickness and mfERG measures of RGC function can be complementary tools in assessing glaucomatous neuropathy.