Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

Congenital Cataracts and Microphakia with Retinal Dysplasia and Optic Nerve Hypoplasia in a Calf

Case Description. A two-month-old, female, Aberdeen-Angus calf was presented for congenital cataracts and blindness in both eyes (OU). The dam had a reported history of visual defects (not specified) and had produced other affected calves (per owner history). Ophthalmic examination revealed mature bilateral cataracts, attenuation of the iridic granules, persistent pupillary membranes, and dyscoric pupils. Additionally, the calf had a poor body condition, prognathism, dome-shaped head, excessive nasal drainage, limb contracture, and fever. Histopathology of both eyes revealed lenticular degeneration (congenital cataracts), retinal dysplasia, and optic nerve hypoplasia. BVDV IHC detected antigen within only the left eye (OS), consisting of intrahistiocytic and endothelial immunoreactivity within the ciliary body, iris, and choroid. No BVDV immunoreactivity could be detected in the right eye (OD). This case highlights the unique ocular changes present in in utero BVDV infection of cattle with a different immunohistochemical staining profile than previously described.

The Incoherent Fluctuation of Folate Pools and Differential Regulation of Folate Enzymes Prioritize Nucleotide Supply in the Zebrafish Model Displaying Folate Deficiency-Induced Microphthalmia and Visual Defects

Graphical AbstractFolate deficiency lowered intracellular 10-CHO-THF and 5-CH3-THF levels, interfered nucleotide formation, impaired cell proliferation, induced apoptosis and impeded vitamin A supply, leading to microphthalmia and obstructed visual ability.

Visual Field Test With Gaze Check Tasks: Application in a Homonymous Hemianopic Patient Unaware of the Visual Defects

Gaze control is required for applying visual stimuli to a particular area of the visual field. We developed a visual field test with gaze check tasks to investigate hemianopia. In this test, participants must report the presence or absence of visual stimuli when a small object at the fixation point vibrates. Trials in the absence of visual stimuli were used as gaze check tasks, since the vibration could be observed only when the gaze was directed at the fixation point. We evaluated the efficacy of our test in four control participants and one patient with homonymous hemianopia who was unaware of the defects in the left visual field. This patient presented hemianopia in the test with gaze check tasks, but not when the gaze check tasks were omitted. The patient showed spontaneous gaze movements from the fixation point to the upper left direction, as well as scanning of the left visual field during the test without gaze check tasks. Thus, we concluded that the visual defects in this patient were compensated in daily life by spontaneous eye movements coordinated with visual information processing. The present results show the usefulness of the visual field test with gaze check tasks.

Commentary review on peripapillary morphological characteristics in high myopia eyes with glaucoma: diagnostic challenges and strategies

The incidences of open angle glaucoma (OAG) and high myopia are increasing concomitantly. Considering the aging population and concurrent rapid increase in the number of individuals with myopia, the risk of visual defects caused by highly myopic OAG is likely to increase dramatically over the next few decades. However, precise screening and diagnosis of OAG is challenging because of the tilt and rotation of the optic disc, as well as extensive β-zone parapapillary atrophy in highly myopic eyes. Recent advances in optical coherence tomography (OCT) and OCT angiography (OCTA) technologies imply that both modalities are promising tools for the detection of highly myopic OAG. Notably, the diagnosis of OAG remains to be determined with the longitudinal changes of functional damages (e.g. visual field defect, visual electrophysiological changes). We herein describe some aspects of microvascular and microstructural pathology in patients with highly myopic OAG and proposes a framework for the development of novel diagnostic and therapeutic strategies.

Ophthalmic Anthropometry among Rural Dwellers in Mashonaland Central Province, Zimbabwe

Introduction The measures of ophthalmic anthropometric parameters may vary among races and ethnic groups but are of immense importance in clinical diagnosis and management of oculo-visual defects. There is paucity of data on these measures among the Zimbabwean population. Purpose The aim was to determine ophthalmic anthropometric parameters among rural dwellers in Zimbabwe. Methods Six ophthalmic anthropometric parameters including interpupillary distance (IPD), head width (HW), temple width (TW), length to bend (LTB), and apical radius were measured using a pupillometer, PD rule, Head width calipers, Fairbank facial gauge, and ABDO frame rule. Results A total of 471 participants aged 18 to 100 years (mean age = 55.13; SD± 17.33 years). Of the 471 participants, 206 (43.7%) were males and 265 (56.3%) were females. A mean interpupillary distance at far was 65.57 ± 4.80 mm, mean temple width of 12.49 ± 1.53 cm, mean head width of 13.61 ± 1.39 cm and a side length to bend of 10.24 ± 1.20 cm and the apical radius was 9.94 ± 1.37. There was a significant (P < 0.05) difference between the ophthalmic anthropometric parameters of males and females except for temple width and apical radius. Conclusion A narrower interpupillary distance but a wider temple width was observed among adult Zimbabweans. A significant difference in ophthalmic anthropometric parameters between males and females were observed except for temple width and apical radius. This should inform eyewear manufacturers and importers of frames on the facial and ocular parameters of Zimbabweans to improve the aesthetics and ensure a comfortable vision for wearers of already-made near vision spectacles for presbyopes. Rwanda J Med Health Sci 2021;4(1):99-111

Functional Role of the RNA-Binding Protein Rbm24a and Its Target sox2 in Microphthalmia

Congenital eye defects represent a large class of disorders affecting roughly 21 million children worldwide. Microphthalmia and anophthalmia are relatively common congenital defects, with approximately 20% of human cases caused by mutations in SOX2. Recently, we identified the RNA-binding motif protein 24a (Rbm24a) which binds to and regulates sox2 in zebrafish and mice. Here we show that morpholino knockdown of rbm24a leads to microphthalmia and visual impairment. By utilizing sequential injections, we demonstrate that addition of exogenous sox2 RNA to rbm24a-deplete embryos is sufficient to suppress morphological and visual defects. This research demonstrates a critical role for understanding the post-transcriptional regulation of genes needed for development.

Interphotoreceptor Retinol-Binding Protein Ameliorates Diabetes-induced Retinal Dysfunction and Neurodegeneration through Rhodopsin

Diabetic patients often experience visual defects before any retinal pathologies are detected. The molecular mechanism for the visual defects in early diabetes has not been elucidated. Our previous study reported that in early diabetic retinopathy (DR), rhodopsin levels were reduced due to impaired 11-<i>cis</i>-retinal regeneration. Interphotoreceptor retinol-binding protein (IRBP) is a visual cycle protein and important for 11-<i>cis</i>-retinal generation. IRBP levels are decreased in the vitreous and retina of DR patients and animal models. To determine the role of IRBP downregulation in the visual defects in early DR, we induced diabetes in transgenic mice overexpressing IRBP in the retina. IRBP overexpression prevented diabetes-induced decline of retinal function. Furthermore, IRBP overexpression also prevented decreases of rhodopsin levels and 11-<i>cis</i>-retinal generation in diabetic mice. Diabetic IRBP transgenic mice also showed ameliorated retinal oxidative stress, inflammation, apoptosis, and retinal degeneration, compared to diabetic WT mice. These findings suggest that diabetes-induced IRBP downregulation impairs the regeneration of 11-<i>cis</i>-retinal and rhodopsin, leading to retinal dysfunction in early DR. Furthermore, increased 11-<i>cis</i>-retinal-free opsin constitutively activates the phototransduction pathway, leading to increased oxidative stress and retinal neurodegeneration. Therefore, restored IRBP expression in the diabetic retina may confer a protective effect against retinal degeneration in DR.

Interphotoreceptor Retinol-Binding Protein Ameliorates Diabetes-induced Retinal Dysfunction and Neurodegeneration through Rhodopsin

Diabetic patients often experience visual defects before any retinal pathologies are detected. The molecular mechanism for the visual defects in early diabetes has not been elucidated. Our previous study reported that in early diabetic retinopathy (DR), rhodopsin levels were reduced due to impaired 11-<i>cis</i>-retinal regeneration. Interphotoreceptor retinol-binding protein (IRBP) is a visual cycle protein and important for 11-<i>cis</i>-retinal generation. IRBP levels are decreased in the vitreous and retina of DR patients and animal models. To determine the role of IRBP downregulation in the visual defects in early DR, we induced diabetes in transgenic mice overexpressing IRBP in the retina. IRBP overexpression prevented diabetes-induced decline of retinal function. Furthermore, IRBP overexpression also prevented decreases of rhodopsin levels and 11-<i>cis</i>-retinal generation in diabetic mice. Diabetic IRBP transgenic mice also showed ameliorated retinal oxidative stress, inflammation, apoptosis, and retinal degeneration, compared to diabetic WT mice. These findings suggest that diabetes-induced IRBP downregulation impairs the regeneration of 11-<i>cis</i>-retinal and rhodopsin, leading to retinal dysfunction in early DR. Furthermore, increased 11-<i>cis</i>-retinal-free opsin constitutively activates the phototransduction pathway, leading to increased oxidative stress and retinal neurodegeneration. Therefore, restored IRBP expression in the diabetic retina may confer a protective effect against retinal degeneration in DR.