Extracellular vesicles (EV), which include exosomes and microvesicles, are secreted from virtually every cell. EV contain mRNA, miRNA, lipids and proteins and can deliver this expansive cargo into nearby cells as well as over long distances via the blood stream. Great interest has been given to them for their role in cell to cell communication, disease progression, or as biomarkers, and more recent

The retinal pigment epithelium (RPE), a monolayer of post-mitotic polarized epithelial cells, strategically situated between the photoreceptors and the choroid, is the primary caretaker of photoreceptor health and function. Dysfunction of the RPE underlies many inherited and acquired diseases that cause permanent blindness. Decades of research have yielded valuable insight into the cell biology of

When analyzing vitreal drug delivery, or the pharmacological effects of drugs on intraocular pressure, or when interpreting outflow facility measurements, it is generally accepted that the fluid in the vitreous humor is stagnant. It is accepted that for all practical purposes, the aqueous fluid exits the eye via anterior pathways only, and so there is negligible if any posteriorly directed flow of

This review summarises our current knowledge of primate including human retina focusing on bipolar, amacrine and ganglion cells and their connectivity. We have two main motivations in writing. Firstly, recent progress in non-invasive imaging methods to study retinal diseases mean that better understanding of the primate retina is becoming an important goal both for basic and for clinical sciences.

Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor-β-induced gene (TGFBI) are associated with amyloid

The core mechanism of dry eye is the tear film instability. Tear film-oriented diagnosis (TFOD) is a concept to clarify the cause of tear film instability by tear film, and tear film-oriented treatment (TFOT) is a concept to treat dry eye disease by replacing the lacking components of the tear film layer based on the TFOD. In TFOD, the fluorescein breakup pattern of the tear film is important, and

Alterations in ocular blood flow have been identified as important risk factors for the onset and progression of numerous diseases of the eye. In particular, several population-based and longitudinal-based studies have provided compelling evidence of hemodynamic biomarkers as independent risk factors for ocular disease throughout several different geographic regions. Despite this evidence, the relative

The choroid is one of the most vascularized structures of the human body and plays an irreplaceable role in nourishing photoreceptors. As such, choroidal dysfunction is implicated in a multitude of ocular diseases. Studying the choroid can lead to a better understanding of disease pathogenesis, progression and discovery of novel management strategies. However, current research has produced inconsistent

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

Age-related diseases, including age-related macular degeneration (AMD), are of growing importance in a world where population ageing has become a dominant global trend. Although a wide variety of risk factors for AMD have been identified, age itself remains by far the most important risk factor, making it an urgent priority to understand the connections between underlying ageing mechanisms and pathophysiology

Due to improved phenotyping and genetic characterization, the field of 'incurable' and 'blinding' inherited retinal diseases (IRDs) has moved substantially forward. Decades of ascertainment of IRD patient data from Philadelphia and Toronto centers illustrate the progress from Mendelian genetic types to molecular diagnoses. Molecular genetics have been used not only to clarify diagnoses and to direct

Known to occur in widespread outbreaks, epidemic keratoconjunctivitis (EKC) is a severe ocular surface infection with a strong historical association with human adenovirus (HAdV). While the conjunctival manifestations can vary from mild follicular conjunctivitis to hyper-acute, exudative conjunctivitis with formation of conjunctival membranes, EKC is distinct as the only form of adenovirus conjunctivitis

Degeneration of specific retinal neurons in diseases like glaucoma, age-related macular degeneration, and retinitis pigmentosa is the leading cause of irreversible blindness. Currently, there is no therapy to modify the disease-associated degenerative changes. With the advancement in our knowledge about the mechanisms that regulate the development of the vertebrate retina, the approach to treat blinding

This paper reviews current knowledge of the evolution of the multiple genes encoding proteins that mediate the process of phototransduction in rod and cone photoreceptors of vertebrates. The approach primarily involves molecular phylogenetic analysis of phototransduction protein sequences, combined with analysis of the syntenic arrangement of the genes. At least 35 of these phototransduction genes

Contact lenses represent a widely utilized form of vision correction with more than 140 million wearers worldwide. Although generally well-tolerated, contact lenses can cause corneal infection (microbial keratitis), with an approximate annualized incidence ranging from ∼2 to ∼20 cases per 10,000 wearers, and sometimes resulting in permanent vision loss. Research suggests that the pathogenesis of contact

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability

Corneal transplantation is the most successful solid organ transplantation performed in humans. The extraordinary success of orthotopic corneal allografts, in both humans and experimental animals, is related to the phenomenon of “immune privilege”. Inflammation is self-regulated to preserve ocular functions because the eye has immune privilege. At present, three major mechanisms are considered to provide

Masquerade syndromes represent a large set of ophthalmological entities that mimic inflammatory conditions. Any delay in their diagnosis may be correlated with systemic dissemination or worsening of the causal disease and, therefore, with poor prognosis. One of the disadvantages of the new potent treatments of uveitis is the delay that they can induce in the diagnosis of neoplastic intraocular infiltrations

Diabetic retinopathy (DR) is one of the leading causes of visual impairment in the working-age population. DR is a progressive eye disease caused by long-term accumulation of hyperglycaemia-mediated pathological alterations in the retina of diabetic patients. DR begins with asymptomatic retinal abnormalities and may progress to advanced-stage proliferative diabetic retinopathy (PDR), characterized

In this review, we summarize studies investigating the types and distribution of voltage- and calcium-gated ion channels in the different classes of retinal neurons: rods, cones, horizontal cells, bipolar cells, amacrine cells, interplexiform cells, and ganglion cells. We discuss differences among cell subtypes within these major cell classes, as well as differences among species, and consider how

The cellular mechanisms underlying hereditary photoreceptor degeneration are still poorly understood, a problem that is exacerbated by the enormous genetic heterogeneity of this disease group. However, the last decade has yielded a wealth of new knowledge on degenerative pathways and their diversity. Notably, a central role of cGMP-signalling has surfaced for photoreceptor cell death triggered by a

The cholinergic system has a crucial role to play in visual function. Although cholinergic drugs have been a focus of attention as glaucoma medications for reducing eye pressure, little is known about the potential modality for neuronal survival and/or enhancement in visual impairments. Citicoline, a naturally occurring compound and FDA approved dietary supplement, is a nootropic agent that is recently

Retinal remodeling is a progressive series of negative plasticity revisions that arise from retinal degeneration, and are seen in retinitis pigmentosa, age-related macular degeneration and other forms of retinal disease. These processes occur regardless of the precipitating event leading to degeneration. Retinal remodeling then culminates in a late-stage neurodegeneration that is indistinguishable

Central serous chorioretinopathy (CSC) is a common cause of central vision loss, primarily affecting men 20-60 years of age. To date, no consensus has been reached regarding the classification of CSC, and a wide variety of interventions have been proposed, reflecting the controversy associated with treating this disease. The recent publication of appropriately powered randomised controlled trials such

Axonal degeneration is an active, highly controlled process that contributes to beneficial processes, such as developmental pruning, but also to neurodegeneration. In glaucoma, ocular hypertension leads to vision loss by killing the output neurons of the retina, the retinal ganglion cells (RGCs). Multiple processes have been proposed to contribute to and/or mediate axonal injury in glaucoma, including:

In the past decade, novel lamellar keratoplasty techniques such as Deep Anterior Lamellar Keratoplasty (DALK) for anterior keratoplasty and Descemet stripping automated endothelial keratoplasty (DSAEK)/Descemet membrane endothelial keratoplasty (DMEK) for posterior keratoplasty have been developed. DALK eliminates the possibility of endothelial allograft rejection, which is the main reason for graft

Dysfunction and loss of the retinal pigment epithelium (RPE) are hallmarks of retinal degenerative diseases in mammals. A critical transcription factor for RPE development and function is the microphthalmia-associated transcription factor MITF and its germline mutations are associated with clinically distinct disorders, including albinism, microphthalmia, retinal degeneration, and increased risk of

Compression of the optic chiasm causes an optic neuropathy that may be associated with reversible visual loss often immediately following surgical decompression. While the precise pathogenesis of retinal ganglion cell impairment and eventual death remains poorly understood, a number of putative mechanisms may play a role. In this article we review the evidence supporting various stages of visual loss

Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation

Bacterial infection of the posterior segment of the eye (endophthalmitis) leads to a robust host response that often results in irreversible damage to the layers of the retina, significant vision loss, and in some patients, enucleation of the globe. While a great deal of effort has gone into understanding the role of bacterial virulence factors in disease initiation and propagation, it is becoming

The cornea is the most sensitive structure in the human body. Corneal nerves adapt to maintain transparency and contribute to corneal health by mediating tear secretion and protective reflexes and provide trophic support to epithelial and stromal cells. The nerves destined for the cornea travel from the trigeminal ganglion in a complex and coordinated manner to terminate between and within corneal

The ocular lens is a unique tissue that contains an age gradient of cells and proteins ranging from newly differentiated cells containing newly synthesized proteins to cells and proteins that are as old as the organism. Thus, the ocular lens is an excellent model for studying long-lived proteins (LLPs) and the effects of aging and post-translational modifications on protein structure and function.

The three interacting components of the outer blood-retinal barrier are the retinal pigment epithelium (RPE), choriocapillaris, and Bruch’s membrane, the extracellular matrix that lies between them. Although previously reviewed independently, this review integrates these components into a more wholistic view of the barrier and discusses reconstitution models to explore the interactions among them.

Glaucoma, an irreversible blinding condition affecting 3-4% adults aged above 40 years worldwide, is set to increase with a rapidly aging global population. Raised intraocular pressure (IOP) is a major risk factor for glaucoma where the treatment paradigm is focused on managing IOP using medications, laser, or surgery regimens. However, notwithstanding IOP and other clinical parameters, patient-reported

Melatonin is not only synthesized by the pineal gland but by several ocular structures. This natural indoleamine is of great importance for regulating several eye processes, among which pressure homeostasis is included. Glaucoma, the most prevalent eye disease, also known as the silent thief of vision, is a multifactorial pathology that is associated to age and, often, to intraocular hypertension (IOP)

The blood-retinal barrier (BRB) plays an important role in the homeostatic regulation of the microenvironment in the retina. It consists of inner and outer components, the inner BRB (iBRB) being formed by the tight junctions between neighbouring retinal capillary endothelial cells and the outer barrier (oBRB) by tight junctions between retinal pigment epithelial cells. Astrocytes, Müller cells and

Intraocular delivery of anti-vascular endothelial growth factor (VEGF) therapies is now used widely to treat age-related macular degeneration, and is currently undergoing evaluation in clinical trials for treatment of diabetic retinopathy. An important aspect of anti-VEGF treatment is that while the agents are injected into the vitreous cavity, they may be absorbed systemically, thus potentially affecting

Mitochondria are central to retinal cell function and survival. There is increasing evidence to support an association between mitochondrial dysfunction and a number of retinal pathologies including age-related macular degeneration (AMD), diabetic retinopathy and glaucoma. The past decade has highlighted mitochondrial genomic instability as an important factor in mitochondrial impairment culminating

Cells of the human retinal pigment epithelium (RPE) have a regular epithelial cell shape within the tissue in situ, but for reasons that remain elusive the RPE shows an incomplete and variable ability to re-develop an epithelial phenotype after propagation in vitro. In other epithelial cell cultures, formation of an adherens junction (AJ) composed of E-cadherin plays an important early inductive role

By most standard engineering practice principles, it is premature to credibly discuss the "engineering" of a human cornea. A professional design engineer would assert that we still do not know what a cornea is (and correctly so), therefore we cannot possibly build one. The proof resides in the fact that there are no clinically viable corneas based on classical tissue engineering methods available.

The active component of the marijuana plant Cannabis sativa, Delta9-tetrahydrocannabinol (THC), produces numerous beneficial effects, including analgesia, appetite stimulation and nausea reduction, in addition to its psychotropic effects. THC mimics the action of endogenous fatty acid derivatives, referred to as endocannabinoids. The effects of THC and the endocannabinoids are mediated largely by metabotropic

The advances in retinal imaging technologies have led to enormous innovation towards diagnostic in current ophthalmology, enabling the practitioner to detect early retinal changes and to document treatment effects. While, in the past, retinoscopy, visual acuity testing and perimetry played the major role in functional diagnostics, today, laser-based systems like laser scanning imaging systems especially

Experimental autoimmune uveoretinitis (EAU) serves as an animal model for human uveitis. EAU is inducible in animals by peripheral immunization with proteins found in the retina that triggers an immune response which leads to tissue damage. This is coordinated by autoantigen specific CD4(+) T cells whose activation is accompanied by the infiltration of a wide range of other leukocytes into the retina

Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the US, for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF)

Leber congenital amaurosis (LCA) is the most severe retinal dystrophy causing blindness or severe visual impairment before the age of 1 year. Linkage analysis, homozygosity mapping and candidate gene analysis facilitated the identification of 14 genes mutated in patients with LCA and juvenile retinal degeneration, which together explain approximately 70% of the cases. Several of these genes have also

Age-related macular degeneration (AMD) is a multifaceted disease characterized by early subclinical changes at the choroidea-retinal pigment epithelium interface. Both the causal and formal pathogenesis of the disease is still puzzling. Similarly, the reason for progression into two distinct late forms which are "geographic atrophy" and "choroidal neovascularization" remains enigmatic. Late changes

Synaptic transmission from photoreceptors to all types of ON bipolar cells is primarily mediated by the mGluR6 receptor. This receptor, which is apparently expressed uniquely in the nervous system by ON bipolar cells, couples negatively to a nonselective cation channel. This arrangement results in a sign reversal at photoreceptor/ON bipolar cell synapse, which is necessary in order to establish parallel

The aquaporins (AQPs) are integral membrane proteins whose main function is to transport water across cell membranes in response to osmotic gradients. At the ocular surface, AQP1 is expressed in corneal endothelium, AQP3 and AQP5 in corneal epithelium, and AQP3 in conjunctival epithelium. AQPs are also expressed in lens fiber cells (AQP0), lens epithelium (AQP1), ciliary epithelium (AQP1, AQP4) and

Developments in optical coherence tomography (OCT) have expanded its clinical applications for high-resolution imaging of the retina, as a standalone diagnostic and in combination with other optical imaging modalities. This review presents currently explored combinations of OCT technology with a variety of complementary imaging modalities along with augmentational technologies such as adaptive optics

Molecular chaperones facilitate and regulate protein conformational change within cells. This encompasses many fundamental cellular processes: including the correct folding of nascent chains; protein transport and translocation; signal transduction and protein quality control. Chaperones are, therefore, important in several forms of human disease, including neurodegeneration. Within the retina, the

Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, as well as intact blood-retinal barriers are necessary requirements for the maintenance

Patterns in nature have always fascinated human beings. They convey the idea of order, organization and optimization, and, to the enquiring mind, the alluring promise that understanding their building rules may uncover the forces that shaped them. In the retina, two patterns are outstanding: the stacking of cells in layers and, within the layers, the prevalent arrangement of neurons of the same type

Changes in the intracellular Ca2+ concentration regulate the visual signal transduction cascade directly or more often indirectly through Ca2+-binding proteins. Here we focus on centrins, which are members of a highly conserved subgroup of the EF-hand superfamily of Ca2+-binding proteins in photoreceptor cells of the vertebrate retina. Centrins are commonly associated with centrosome-related structures