Browsing by Subject "Vision"
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Item Circadian Rhythm Disruption Results in Visual Dysfunction(Wiley, 2022-02-07) Mathew, Deepa; Luo, Qianyi; Bhatwadekar, Ashay D.; Ophthalmology, School of MedicineArtificial light has been increasingly in use for the past 70 years. The aberrant light exposure and round‐the‐clock nature of work lead to the disruption of biological clock. Circadian rhythm disruption (CRD) contributes to multiple metabolic and neurodegenerative diseases. However, its effect on vision is not understood. Moreover, the mammalian retina possesses an autonomous clock that could be reset with light exposure. We evaluated the impact of CRD on retinal morphology, physiology, and vision after housing mice in a disruption inducing shorter light/dark cycle (L10:D10). Interestingly, the mice under L10:D10 exhibited three different entrainment behaviors; “entrained,” “free‐running,” and “zigzagging.” These behavior groups under CRD exhibited reduced visual acuity, retinal thinning, and a decrease in the number of photoreceptors. Intriguingly, the electroretinogram response was decreased only in the mice exhibiting “entrained” behavior. The retinal proteome showed distinct changes with each entrainment behavior, and there was a dysfunctional oxidative stress‐antioxidant mechanism. These results demonstrate that CRD alters entrainment behavior and leads to visual dysfunction in mice. Our studies uniquely show the effect of entrainment behavior on retinal physiology. Our data have broader implications in understanding and mitigating the impact of CRD on vision and its potential role in the etiology of retinal diseases.Item Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina(Springer Nature, 2025-01-30) Weekman, Erica M.; Rogers, Colin B.; Sudduth, Tiffany L.; Wilcock, Donna M.; Neurology, School of MedicineOver recent years, the retina has been increasingly investigated as a potential biomarker for dementia. A number of studies have looked at the effect of Alzheimer's disease (AD) pathology on the retina and the associations of AD with visual deficits. However, while OCT-A has been explored as a biomarker of cerebral small vessel disease (cSVD), studies identifying the specific retinal changes and mechanisms associated with cSVD are lacking. Using our model of hyperhomocysteinemia-induced cSVD, we aimed to identify the effects of cSVD on visual sensitivity and cognition, retinal glial and vascular cells, and neuroinflammatory and cardiovascular gene expression changes. We placed C57Bl6/SJL mice on a HHcy-inducing diet, a model that has been well characterized to have vascular pathologies in the brain similar to pathologic cSVD. After 14 weeks on diet, mice underwent the Visual-Stimuli 4-arm Maze to identify visual deficits. Whole mount retinas were stained for vessels, microglia and astrocytes to identify glial and vascular changes. Finally, neuroinflammatory and cardiovascular gene expression was measured using NanoString's nCounter system. Ultimately, HHcy led to visual changes that specifically affected the reaction to blue and white light, slightly decreased vascular volume and significantly decreased interaction of microglia with the vasculature, as well as downregulation of inflammatory and vascular genes. These changes provide novel insights and reproduce some prior observations. These studies highlight retinal changes in association with cSVD and serve as a precaution when interpreting vision-dependent cognitive testing of cSVD models.Item Induction of VCID via hyperhomocysteinemia leads to vision and retina changes in mice(Wiley, 2025-01-03) Weekman, Erica M.; Rogers, Colin B.; Sudduth, Tiffany L.; Wilcock, Donna M.; Neurology, School of MedicineBackground: Diagnosis of Alzheimer’s disease (AD) via MRI is costly and can be limited by regional availability. With the recent advancements and discovery of amyloid in the retina, diagnosis of AD and the effect of AD pathology on the retina is becoming well characterized. However, the prevalence of vascular contributions to cognitive impairment and dementia (VCID) and its effects on the retina are less well known. With the retina being a highly vascularized tissue and the considerable overlap of AD with VCID, it is imperative to understand the effect of VCID on vision. Method: We placed 6‐month‐old mice on a diet deficient in B vitamins and enriched in methionine to induce hyperhomocysteinemia (HHcy). HHcy is a risk factor for VCID, stroke and AD, and has been well characterized in our lab. After 14 weeks on diet, mice underwent the Visual‐Stimuli 4‐arm Maze (ViS4M) to identify visual and cognitive abnormalities. After behavior, brains and eyes were harvested with the left eye fixed in 4% PFA for 24hrs and the right eye flash frozen for RNA extraction. The fixed retina was flat mounted and stained for vessels, GFAP, and IBA‐1 and the flash frozen retina was used for RNA isolation and NanoString analysis. Result: Over the seven days the mice were tested on the ViS4M, the mice on the HHcy diet showed impaired cognition and altered colored arm entries compared to control mice. HHcy mice made more 2 arm alternations than 3 or 4 arm alternations, suggesting diminished exploration. When we determined their arm transitions, we saw that the HHcy mice tended to avoid the blue arm, suggesting sensitivity to blue light. In the retina, we saw slightly less vessel volume in the HHcy diet mice along with reduced coverage of vessels by microglia and astrocytes combined. Conclusion: The high prevalence of VCID with AD along with the impact of AD pathology on the eye makes it critical to understand the effect of VCID on the retina. In our model of HHcy induced VCID, we determined that HHcy does impair both cognition and vision and affects vessels within the retina.Item Leveraging the power of partnerships: spreading the vision for a population health care delivery model in western Kenya(BMC, 2018-05-08) Mercer, Tim; Gardner, Adrian; Andama, Benjamin; Chesoli, Cleophas; Christoffersen-Deb, Astrid; Dick, Jonathan; Einterz, Robert; Gray, Nick; Kimaiyo, Sylvester; Kamano, Jemima; Maritim, Beryl; Morehead, Kirk; Pastakia, Sonak; Ruhl, Laura; Songok, Julia; Laktabai, Jeremiah; Medicine, School of MedicineBACKGROUND: The Academic Model Providing Access to Healthcare (AMPATH) has been a model academic partnership in global health for nearly three decades, leveraging the power of a public-sector academic medical center and the tripartite academic mission - service, education, and research - to the challenges of delivering health care in a low-income setting. Drawing our mandate from the health needs of the population, we have scaled up service delivery for HIV care, and over the last decade, expanded our focus on non-communicable chronic diseases, health system strengthening, and population health more broadly. Success of such a transformative endeavor requires new partnerships, as well as a unification of vision and alignment of strategy among all partners involved. Leveraging the Power of Partnerships and Spreading the Vision for Population Health. We describe how AMPATH built on its collective experience as an academic partnership to support the public-sector health care system, with a major focus on scaling up HIV care in western Kenya, to a system poised to take responsibility for the health of an entire population. We highlight global trends and local contextual factors that led to the genesis of this new vision, and then describe the key tenets of AMPATH's population health care delivery model: comprehensive, integrated, community-centered, and financially sustainable with a path to universal health coverage. Finally, we share how AMPATH partnered with strategic planning and change management experts from the private sector to use a novel approach called a 'Learning Map®' to collaboratively develop and share a vision of population health, and achieve strategic alignment with key stakeholders at all levels of the public-sector health system in western Kenya. CONCLUSION: We describe how AMPATH has leveraged the power of partnerships to move beyond the traditional disease-specific silos in global health to a model focused on health systems strengthening and population health. Furthermore, we highlight a novel, collaborative tool to communicate our vision and achieve strategic alignment among stakeholders at all levels of the health system. We hope this paper can serve as a roadmap for other global health partners to develop and share transformative visions for improving population health globally.Item MFRP is a molecular hub that organizes the apical membrane of RPE cells by engaging in interactions with specific proteins and lipids(National Academy of Sciences, 2025) Tworak, Aleksander; Smidak, Roman; Rodrigues Menezes, Carolline; Du, Samuel W.; Suh, Susie; Choi, Elliot H.; Imanishi, Sanae S.; Dong, Zhiqian; Lewandowski, Dominik; Fong, Kristen E.; Grigorean, Gabriela; Pinto, Antonio F. M.; Xu, Qianlan; Skowronska-Krawczyk, Dorota; Blackshaw, Seth; Imanishi, Yoshikazu; Palczewski, Krzysztof; Ophthalmology, School of MedicineMembrane frizzled-related protein (MFRP), present in the retinal pigment epithelium (RPE), is an integral membrane protein essential for ocular development and the normal physiology of the retina. Mutations in MFRP are associated with autosomal recessive nonsyndromic nanophthalmos, leading to severe hyperopia and early-onset retinitis pigmentosa. While several preclinical gene-augmentation and gene-editing trials hold promise for future therapies aimed at stopping degeneration and restoring retinal function, the molecular mechanisms involved in MFRP biology are still not well understood. Here, we studied the biochemical properties of MFRP and the molecular consequences of its loss of function in the retinal degeneration 6 (rd6) mouse model. Using transcriptomic and lipidomic approaches, we observed that accumulation of docosahexaenoic acid (DHA) constitutes a primary defect in the MFRP-deficient RPE. In biochemical assays, we showed that MFRP undergoes extensive glycosylation, and it preferentially binds lipids of several classes, including phosphatidylserine and phosphatidylinositol-4-phosphate; as well as binding to several transmembrane proteins, notably adiponectin receptor 1 (ADIPOR1) and inward rectifier potassium channel 13 (KCNJ13). Moreover, MFRP determines the subcellular localization of ADIPOR1 and KCNJ13 in the RPE in vivo. This feature is altered by MFRP deficiency and can be restored by gene-therapy approaches. Overall, our observations suggest that MFRP constitutes an important interaction hub within the apical membrane of RPE cells, coordinating protein trafficking and subcellular localization within the RPE, and lipid homeostasis within the entire retina.Item Signals from posterior parietal area 5 to motor cortex during locomotion(Oxford University Press, 2023) Beloozerova, Irina N.; Nilaweera, Wijitha U.; Di Prisco, Gonzalo Viana; Marlinski, Vladimir; Pharmacology and Toxicology, School of MedicineArea 5 of the parietal cortex is part of the "dorsal stream" cortical pathway which processes visual information for action. The signals that area 5 ultimately conveys to motor cortex, the main area providing output to the spinal cord, are unknown. We analyzed area 5 neuronal activity during vision-independent locomotion on a flat surface and vision-dependent locomotion on a horizontal ladder in cats focusing on corticocortical neurons (CCs) projecting to motor cortex from the upper and deeper cortical layers and compared it to that of neighboring unidentified neurons (noIDs). We found that upon transition from vision-independent to vision-dependent locomotion, the low discharge of CCs in layer V doubled and the proportion of cells with 2 bursts per stride tended to increase. In layer V, the group of 2-bursters developed 2 activity peaks that coincided with peaks of gaze shifts along the surface away from the animal, described previously. One-bursters and either subpopulation in supragranular layers did not transmit any clear unified stride-related signal to the motor cortex. Most CC group activities did not mirror those of their noID counterparts. CCs with receptive fields on the shoulder, elbow, or wrist/paw discharged in opposite phases with the respective groups of pyramidal tract neurons of motor cortex, the cortico-spinal cells.Item Sites of Power and the Power of Sight: Vision in the California Mission Landscapes(University of Pittsburgh Press, 2007) Kryder-Reid, ElizabethThe relationships of sight and power in the landscapes in California missions are explored in this study of three periods of mission history – the sites’ origins as the locus of colonial encounters between Spanish Franciscans and the Indigenous peoples of California, their later re- invention as public sites with “California mission gardens,” and contemporary tourist destinations. While seemingly disparate settings, this paper argues that the imposition of western power on Native peoples and the creation of romanticized oases in tourist destinations are parallel in a number of respects, particularly in the control of vision. The paper also explores diverse perspectives on this view of the land by examining indigenous ideologies of landscape and local expressions of meaning within garden design.Item Visual contrast sensitivity in Alzheimer's disease, mild cognitive impairment, and older adults with cognitive complaints(Elsevier, 2013) Risacher, Shannon L.; WuDunn, Darrell; Pepin, Susan M.; MaGee, Tamiko R.; McDonald, Brenna C.; Flashman, Laura A.; Wishart, Heather A.; Pixley, Heather S.; Rabin, Laura A.; Paré, Nadia; Englert, Jessica J.; Schwartz, Eben; Curtain, Joshua R.; West, John D.; O’Neill, Darren P.; Santulli, Robert B.; Newman, Richard W.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineDeficits in contrast sensitivity (CS) have been reported in Alzheimer's disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.Item Visual contrast sensitivity is associated with the presence of cerebral amyloid and tau deposition(Oxford University Press, 2020) Risacher, Shannon L; WuDunn, Darrell; Tallman, Eileen F.; West, John D.; Gao, Sujuan; Farlow, Martin R.; Brosch, Jared R.; Apostolova, Liana G.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineVisual deficits are common in neurodegenerative diseases including Alzheimer’s disease. We sought to determine the association between visual contrast sensitivity and neuroimaging measures of Alzheimer’s disease-related pathophysiology, including cerebral amyloid and tau deposition and neurodegeneration. A total of 74 participants (7 Alzheimer’s disease, 16 mild cognitive impairment, 20 subjective cognitive decline, 31 cognitively normal older adults) underwent the frequency doubling technology 24-2 examination, a structural MRI scan and amyloid PET imaging for the assessment of visual contrast sensitivity. Of these participants, 46 participants (2 Alzheimer’s disease, 9 mild cognitive impairment, 12 subjective cognitive decline, 23 cognitively normal older adults) also underwent tau PET imaging with [18F]flortaucipir. The relationships between visual contrast sensitivity and cerebral amyloid and tau, as well as neurodegeneration, were assessed using partial Pearson correlations, covaried for age, sex and race and ethnicity. Voxel-wise associations were also evaluated for amyloid and tau. The ability of visual contrast sensitivity to predict amyloid and tau positivity were assessed using forward conditional logistic regression and receiver operating curve analysis. All analyses first were done in the full sample and then in the non-demented at-risk individuals (subjective cognitive decline and mild cognitive impairment) only. Significant associations between visual contrast sensitivity and regional amyloid and tau deposition were observed across the full sample and within subjective cognitive decline and mild cognitive impairment only. Voxel-wise analysis demonstrated strong associations of visual contrast sensitivity with amyloid and tau, primarily in temporal, parietal and occipital brain regions. Finally, visual contrast sensitivity accurately predicted amyloid and tau positivity. Alterations in visual contrast sensitivity were related to cerebral deposition of amyloid and tau, suggesting that this measure may be a good biomarker for detecting Alzheimer’s disease-related pathophysiology. Future studies in larger patient samples are needed, but these findings support the power of these measures of visual contrast sensitivity as a potential novel, inexpensive and easy-to-administer biomarker for Alzheimer’s disease-related pathology in older adults at risk for cognitive decline.