Non-haematopoietic Sca-1 Cells in the Retina of Adult Mice Express Functional TLR2.

The mammal retina does not have the capacity to regenerate throughout life, although some stem and progenitor cells persist in the adult retina and might retain multipotentiality, as previously described in many tissues. In this work we demonstrate the presence of a small lineage Sca-1 cell population in the adult mouse retina which expresses functional TLR2 receptors as in vitro challenge with the pure TLR2 agonist PamCSK increases cell number and upregulates TLR2. Therefore, this population could be of interest in neuroregeneration studies to elucidate its role in these processes.

Ischemia-Reperfusion Increases TRPM7 Expression in Mouse Retinas.

Ischemia is the main cause of cell death in retinal diseases such as vascular occlusions, diabetic retinopathy, glaucoma, or retinopathy of prematurity. Although excitotoxicity is considered the primary mechanism of cell death during an ischemic event, antagonists of glutamatergic receptors have been unsuccessful in clinical trials with patients suffering ischemia or stroke. Our main purpose was to analyze if the transient receptor potential channel 7 (TRPM7) could contribute to retinal dysfunction in retinal pathologies associated with ischemia.

Starburst amacrine cells, involved in visual motion perception, loose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson's disease patients.

Background: The main clinical symptoms characteristic of Parkinson's disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception.

Microglia activation and neuronal alterations in retinas from COVID-19 patients: correlation with clinical parameters.

Background: Different ocular alterations have been described in patients with coronavirus disease 2019 (COVID-19). Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters.

Methods: Retinal sections and flat-mount retinas from human donors with COVID-19 (n = 16) and controls (n = 15) were immunostained.

Purinergic Receptors P2X7 and P2X4 as Markers of Disease Progression in the rd10 Mouse Model of Inherited Retinal Dystrophy.

The purinergic receptor P2X7 (P2X7R) is implicated in all neurodegenerative diseases of the central nervous system. It is also involved in the retinal degeneration associated with glaucoma, age-related macular degeneration, and diabetic retinopathy, and its overexpression in the retina is evident in these disorders. Retinitis pigmentosa is a progressive degenerative disease that ultimately leads to blindness.

Cellular and molecular alterations in neurons and glial cells in inherited retinal degeneration.

Multiple gene mutations have been associated with inherited retinal dystrophies (IRDs). Despite the spectrum of phenotypes caused by the distinct mutations, IRDs display common physiopathology features. Cell death is accompanied by inflammation and oxidative stress.

Combined drug triads for synergic neuroprotection in retinal degeneration.

This review focuses on retina degeneration occurring during glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), and on the potential therapeutic use of triads of repositioned medicines, addressed to distinct but complementary targets, to prevent, delay or stop retina cell death. Although myriad pathogenic mechanisms have been implicated in these disorders, common signaling pathways leading to apoptotic cell death to all of them, and to all neurodegenerative diseases are (i) calcium dyshomeostasis/excitotoxicity; (ii) oxidative stress/mitochondrial dysfunction, and (iii) neuroinflammation/P2X7 receptor activation. From a therapeutic point of view, it is relevant to consider the multitarget approach based on the use of combined medicines acting on complementary pathogenic mechanisms that has been highly successful in the treatment of chronic diseases such as cancer, AIDS, pain, hypertension, Parkinson's disease, cardiac failure, depression, or the epilepsies as the basic mechanisms of cell death do not differ between the different CNS degenerative diseases.

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications.

Inherited retinal dystrophies (IRDs) are a large group of genetically and clinically heterogeneous diseases characterized by the progressive degeneration of the retina, ultimately leading to loss of visual function. Oxidative stress and inflammation play fundamental roles in the physiopathology of these diseases. Photoreceptor cell death induces an inflammatory state in the retina.

Sodium Hyaluronate-Induced Ocular Hypertension in Rats Damages the Direction-Selective Circuit and Inner/Outer Retinal Plexiform Layers.

Purpose: To assess the changes in retinal morphology in a rat model of chronic glaucoma induced by ocular hypertension.

Methods: Intraocular pressure (IOP) was surgically increased through weekly injections of sodium hyaluronate (HYA) in the anterior eye chamber of the left eye of male Wistar rats, whereas the right eyes were sham operated (salt solution). During the 10-week experimental period, IOP was measured weekly with a rebound tonometer.

Neuroprotective Effects of Tauroursodeoxicholic Acid Involves Vascular and Glial Changes in Retinitis Pigmentosa Model.

Purpose: Retinitis pigmentosa is primarily characterized by a massive photoreceptor loss. But a global retinal remodeling occurs in later stages of the disease. At that phase, glial cells and retinal vasculature are also strongly affected.

Short-term high-fat feeding exacerbates degeneration in retinitis pigmentosa by promoting retinal oxidative stress and inflammation.

A high-fat diet (HFD) can induce hyperglycemia and metabolic syndromes that, in turn, can trigger visual impairment. To evaluate the acute effects of HFD feeding on retinal degeneration, we assessed retinal function and morphology, inflammatory state, oxidative stress, and gut microbiome in dystrophic retinal degeneration 10 (rd10) mice, a model of retinitis pigmentosa, fed an HFD for 2 to 3 wk. Short-term HFD feeding impaired retinal responsiveness and visual acuity and enhanced photoreceptor degeneration, microglial cell activation, and Müller cell gliosis.

Decrease in DHA and other fatty acids correlates with photoreceptor degeneration in retinitis pigmentosa.

Fatty acids, and especially docosahexaenoic acid (DHA), are essential for photoreceptor cell integrity and are involved in the phototransduction cascade. In this study, we analyzed the changes in the fatty acid profile in the retina of the rd10 mouse, model of retinitis pigmentosa, in order to identify potential risk factors for retinal degeneration and possible therapeutic approaches. Fatty acids from C57BL/6J and rd10 mouse retinas were extracted with Folch's method and analyzed by gas chromatography/mass spectrometry.

Retinitis pigmentosa is associated with shifts in the gut microbiome.

The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP). Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retinal degeneration and gut microbiome in the rd10 mouse model of RP as compared to control C57BL/6J mice.

Dopaminergic Retinal Cell Loss and Visual Dysfunction in Parkinson Disease.

Objective: Considering the demonstrated implication of the retina in Parkinson disease (PD) pathology and the importance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic amacrine cells and some of their main postsynaptic neurons in the retina of PD.

Methods: Using immunohistochemistry and confocal microscopy, we evaluated morphology, number, and synaptic connections of dopaminergic cells and their postsynaptic cells, AII amacrine and melanopsin-containing retinal ganglion cells, in control and PD eyes from human donors.

Results: In PD, dopaminergic amacrine cell number was reduced between 58% and 26% in different retinal regions, involving a decline in the number of synaptic contacts with AII amacrine cells (by 60%) and melanopsin cells (by 35%).

Gradual Increase in Environmental Light Intensity Induces Oxidative Stress and Inflammation and Accelerates Retinal Neurodegeneration.

Purpose: Retinitis pigmentosa (RP) is a blinding neurodegenerative disease of the retina that can be affected by many factors. The present study aimed to analyze the effect of different environmental light intensities in rd10 mice retina.

Methods: C57BL/6J and rd10 mice were bred and housed under three different environmental light intensities: scotopic (5 lux), mesopic (50 lux), and photopic (300 lux).

New Nrf2-Inducer Compound ITH12674 Slows the Progression of Retinitis Pigmentosa in the Mouse Model rd10.

Background/aims: It is well established that oxidative stress and inflammation are common pathogenic features of retinal degenerative diseases. ITH12674 is a novel compound that induces the transcription factor Nrf2; in so doing, the molecule exhibits anti-inflammatory, and antioxidant properties, and affords neuroprotection in rat cortical neurons subjected to oxidative stress. We here tested the hypothesis that ITH12674 could slow the retinal degeneration that causes blindness in rd10 mice, a model of retinitis pigmentosa.

Interpretation of OCT and OCTA images from a histological approach: Clinical and experimental implications.

Optical coherence tomography (OCT) and OCT angiography (OCTA) have been a technological breakthrough in the diagnosis, treatment, and follow-up of many retinal diseases, thanks to its resolution and its ability to inform of the retinal state in seconds, which gives relevant information about retinal degeneration. In this review, we present an immunohistochemical description of the human and mice retina and we correlate it with the OCT bands in health and pathological conditions. Here, we propose an interpretation of the four outer hyperreflective OCT bands with a correspondence to retinal histology: the first and innermost band as the external limiting membrane (ELM), the second band as the cone ellipsoid zone (EZ), the third band as the outer segment tips phagocytosed by the pigment epithelium (PhaZ), and the fourth band as the mitochondria in the basal portion of the RPE (RPEmitZ).

Photosensitive Melanopsin-Containing Retinal Ganglion Cells in Health and Disease: Implications for Circadian Rhythms.

Melanopsin-containing retinal ganglion cells (mRGCs) represent a third class of retinal photoreceptors involved in regulating the pupillary light reflex and circadian photoentrainment, among other things. The functional integrity of the circadian system and melanopsin cells is an essential component of well-being and health, being both impaired in aging and disease. Here we review evidence of melanopsin-expressing cell alterations in aging and neurodegenerative diseases and their correlation with the development of circadian rhythm disorders.

The Absence of Toll-Like Receptor 4 Mildly Affects the Structure and Function in the Adult Mouse Retina.

The innate immune Toll-like receptor (TLR) family plays essential roles in cell proliferation, survival and function of the central nervous system. However, the way in which TLRs contribute to the development and maintenance of proper retinal structure and function remains uncertain. In this work, we assess the effect of genetic TLR4 deletion on the morphology and function of the retina in mice.

Cannabinoid-mediated retinal rescue correlates with improved circadian parameters in retinal dystrophic rats.

Ocular pathologies and blindness have been linked to circadian disorders. In previous studies, our group has demonstrated that retinitis pigmentosa is associated with degenerative changes in the melanopsin system and weaker circadian patterns. We have also shown that cannabinoids preserve retinal structure and function in dystrophic P23H rats.

Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinson's disease.

Parkinson's disease (PD) patients often suffer from non-motor symptoms like sleep dysregulation, mood disturbances or circadian rhythms dysfunction. The melanopsin-containing retinal ganglion cells are involved in the control and regulation of these processes and may be affected in PD, as other retinal and visual implications have been described in the disease. Number and morphology of human melanopsin-containing retinal ganglion cells were evaluated by immunohistochemistry in eyes from donors with PD or control.

Retinal Vascular Degeneration in the Transgenic P23H Rat Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases involving a progressive degeneration of photoreceptor cells. Following the loss of photoreceptors, retinal vascularization tends to decrease, which seems to play a role in the degenerative process of retinal cells. This study reports changes in retinal vascular network architecture in the P23H rat model of RP at different stages of retinal degeneration.