Ocular Metabolism Research Articles

Nanomedicine for the Detection and Treatment of Ocular Bacterial Infections.

Ocular bacterial infection is a prevalent cause of blindness worldwide, with substantial consequences for normal human life. Traditional treatments for ocular bacterial infections are ineffective, necessitating the development of novel techniques to enable accurate diagnosis, precise drug delivery, and effective treatment alternatives. With the rapid advancement of nanoscience and biomedicine, increasing emphasis has been placed on multifunctional nanosystems to overcome the challenges posed by ocular bacterial infections. Given the advantages of nanotechnology in the biomedical industry, it can be utilized to diagnose ocular bacterial infections, administer medications, and treat them. In this review, the recent advancements in nanosystems for the detection and treatment of ocular bacterial infections are discussed; this includes the latest application scenarios of nanomaterials for ocular bacterial infections, in addition to the impact of their essential characteristics on bioavailability, tissue permeability, and inflammatory microenvironment. Through an in-depth investigation into the effect of sophisticated ocular barriers, antibacterial drug formulations, and ocular immune metabolism on drug delivery systems, this review highlights the challenges faced by ophthalmic medicine and encourages basic research and future clinical transformation based on ophthalmic antibacterial nanomedicine. This article is protected by copyright. All rights reserved.

Alterations in ocular microcirculation and oxygen metabolism in patients with lipemia retinalis

PurposeThe study aims to assess the alterations in retinal oxygen saturation and retinal and choroidal blood flow in lipemia retinalis.MethodsThis was a cross-sectional study on 10 eyes (5 patients) with history of lipemia retinalis. The study comprised 10 eyes with documented history of lipemia retinalis and 10 participants as healthy controls. Patients with a confirmed history of lipemia retinalis were grouped into two cohorts based on their most recent fundus examination: untreated lipemia retinalis (abnormal fundus) and resolved lipemia retinalis (normal fundus). Both retinal arteriolar and venular oxygen saturation were measured using the non-invasive spectrophotometric retinal oximeter (Oxymap T1). The mean blur rate (MBR) of the optic nerve and choroidal blood flow were analyzed using a laser speckle flowgraph (LSFG).ResultsPatients with untreated lipemia retinalis had a significantly higher retinal arteriolar and venular oxygen saturation than that of the other two groups (p < 0.001). Moreover, patients with untreated lipemia retinalis had significantly smaller retinal arteriolar and venular diameters (p < 0.001). On LSFG, there was a significant difference in the overall MBR (p = 0.007) and vessel MBR of the optic nerve between the groups (p = 0.011). The patients with history of lipemia retinalis (untreated and resolved) exhibited a high overall MBR and vessel MBR of the optic nerve than that of the control group. There was a significant elevation of the optic nerve (p = 0.002) and choroidal blowout score (p < 0.001), while the resistivity index of the optic nerve (p = 0.001) and choroids (p = 0.002) was significantly lower in patients with resolved and untreated lipemia retinalis.ConclusionsThere was a significant alteration in retinal oximetry, in untreated lipemia retinalis, and in retinal blood flow, in both the resolved and untreated groups. The increase in retinal blood flow and oxygen saturation may elucidate the preservation of visual acuity and function despite the fundus changes observed in lipemia retinalis.

Acute uveitic phase of Vogt-Koyanagi-Harada disease: optic nerve head swelling, ocular blood flow and retinal oxygen metabolism.

To investigate the association of optic nerve head (ONH) swelling in the acute uveitic phase of Vogt-Koyanagi-Harada (VKH) disease with blood flow velocity in the choroid and ONH and oxygen saturation and diameter of retinal vessels. In this prospective study, 25 patients (50 eyes) were studied. Thirteen patients (26 eyes) had ONH swelling and 12 patients (24 eyes) had no ONH swelling. Laser speckle flowgraphy (LSFG) and retinal oximetry measurements were performed at presentation. In the ONH, mean blur rate (MBR)-vessel, representing blood flow velocity in retinal vessels, was significantly lower in the eyes affected by ONH swelling, while choroidal MBR was not significantly different. Eyes with ONH swelling had a significantly lower oxygen saturation in retinal venules, a significantly higher arteriovenous oxygen saturation difference and a significantly smaller calibre of retinal arterioles compared with eyes without ONH swelling. There were significant positive correlations between the MBR-vessel of the ONH and venular oxygen saturation and calibre of retinal arterioles. In addition, MBR-vessel of the ONH had a significant negative correlation with arteriovenous oxygen saturation difference. The occurrence of ONH swelling in the acute uveitic phase of VKH disease is associated with lower retinal blood flow velocity and smaller calibre of retinal arterioles as well as lower oxygen saturation in retinal venules and higher arteriovenous difference in oxygen saturation.

CD73 controls ocular adenosine levels and protects retina from light-induced phototoxicity

ATP and adenosine have emerged as important signaling molecules involved in vascular remodeling, retinal functioning and neurovascular coupling in the mammalian eye. However, little is known about the regulatory mechanisms of purinergic signaling in the eye. Here, we used three-dimensional multiplexed imaging, in situ enzyme histochemistry, flow cytometric analysis, and single cell transcriptomics to characterize the whole pattern of purine metabolism in mouse and human eyes. This study identified ecto-nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39), NTPDase2, and ecto-5′-nucleotidase/CD73 as major ocular ecto-nucleotidases, which are selectively expressed in the photoreceptor layer (CD73), optic nerve head, retinal vasculature and microglia (CD39), as well as in neuronal processes and cornea (CD39, NTPDase2). Specifically, microglial cells can create a spatially arranged network in the retinal parenchyma by extending and retracting their branched CD39high/CD73low processes and forming local “purinergic junctions” with CD39low/CD73− neuronal cell bodies and CD39high/CD73− retinal blood vessels. The relevance of the CD73–adenosine pathway was confirmed by flash electroretinography showing that pharmacological inhibition of adenosine production by injection of highly selective CD73 inhibitor PSB-12489 in the vitreous cavity of dark-adapted mouse eyes rendered the animals hypersensitive to prolonged bright light, manifested as decreased a-wave and b-wave amplitudes. The impaired electrical responses of retinal cells in PSB-12489-treated mice were not accompanied by decrease in total thickness of the retina or death of photoreceptors and retinal ganglion cells. Our study thus defines ocular adenosine metabolism as a complex and spatially integrated network and further characterizes the critical role of CD73 in maintaining the functional activity of retinal cells.

The Effect of Optical Defocus on the Choroidal Thickness: A Review

The choroid is a heavily vascularized tissue located between the retina and sclera and plays a primary role in ocular metabolism. It has recently been suggested that the choroid has the ability to change its thickness and secretion of growth factors. This may play an important role during visual development by adjusting retinal position during growth to support emmetropisation; however, the mechanism by which changes in choroidal thickness (ChT) occur is unclear. This relationship becomes an interesting topic in the clinical field, although conflicting evidence found that these changes in the choroidal thickness may not be associated with the development of refractive errors. Many reports have investigated the changes in the choroid and related factors that affect the ChT. Thus, this review will summarize the current literature related to choroidal thickness in different refractive error groups, determine the factors that influence the thickness of the choroid, and discuss in detail the relationship between the changes in the ChT and ocular elongation, and therefore, the effect of optical defocus on ChT and the development of the refractive error.

Ocular metabolism and distribution of drugs in the rabbit eye: Quantitative assessment after intracameral and intravitreal administrations

Quantitation of ocular drug metabolism is important, but only sparse data is currently available. Herein, the pharmacokinetics of four drugs, substrates of metabolizing enzymes, was investigated in albino rabbit eyes after intracameral and intravitreal administrations. Acetaminophen, brimonidine, cefuroxime axetil, and sunitinib and their corresponding metabolites were quantitated in the cornea, iris-ciliary body, aqueous humor, lens, vitreous humor, and neural retina with LC-MS/MS analytics. Non-compartmental analysis was employed to estimate the pharmacokinetic parameters of the parent drugs and metabolites. The area under the curve (AUC) values of metabolites were 12–70 times lower than the AUC values of the parent drugs in the tissues with the highest enzymatic activity. The ester prodrug cefuroxime axetil was an exception because it was efficiently and quantitatively converted to cefuroxime in the ocular tissues. In contrast to the liver, sulfotransferases, aldehyde oxidase, and cytochrome P450 3A activities were low in the eye and they had negligible impact on ocular drug clearance. With the exception of esterase substrates, metabolism seems to be a minor player in ocular pharmacokinetics. However, metabolites might contribute to ocular toxicity, and drug metabolism in various eye tissues should be investigated and understood thoroughly.

An Analysis of Metabolic Changes in the Retina and Retinal Pigment Epithelium of Aging Mice.

PurposeThe purpose of this study was to present our hypothesis that aging alters metabolic function in ocular tissues. We tested the hypothesis by measuring metabolism in aged murine tissues alongside retinal responses to light.MethodsScotopic and photopic electroretinogram (ERG) responses in young (3–6 months) and aged (23–26 months) C57Bl/6J mice were recorded. Metabolic flux in retina and eyecup explants was quantified using U-13C-glucose or U-13C-glutamine with gas chromatography-mass spectrometry (GC-MS), O2 consumption rate (OCR) in a perifusion apparatus, and quantifying adenosine triphosphatase (ATP) with a bioluminescence assay.ResultsScotopic and photopic ERG responses were reduced in aged mice. Glucose metabolism, glutamine metabolism, OCR, and ATP pools in retinal explants were mostly unaffected in aged mice. In eyecups, glutamine usage in the Krebs Cycle decreased while glucose metabolism, OCR, and ATP pools remained stable.ConclusionsOur examination of metabolism showed negligible impact of age on retina and an impairment of glutamine anaplerosis in eyecups. The metabolic stability of these tissues ex vivo suggests age-related metabolic alterations may not be intrinsic. Future experiments should focus on determining whether external factors including nutrient supply, oxygen availability, or structural changes influence ocular metabolism in vivo.

Comparative Proteomics Analysis of the Post‐Mitochondrial Fraction (S9 Fraction) of Human Lens‐Free Whole Eye and Liver

Background The increasing incidence of ocular diseases has accelerated research into therapeutic interventions for the eye. The knowledge of key metabolic mechanisms in the eye is vital for the successful ophthalmic drug discovery. The lens-free whole-eye post-mitochondrial fraction(S9 fraction) is one of the most widely used in vitro system for ocular metabolism studies during early drug discovery stage. As of now, no report of a comprehensive proteomics investigation exists for the pooled ocular S9 fraction. The objective of this study was to explore the human ocular S9 proteome and compare it with the human liver S9 proteome. Methods The global proteomics study was performed on the pooled ocular (n=11) and hepatic (n=50) S9 fraction samples in data-dependent acquisition mode using an optimized protocol. The samples were acquired in triplicate to minimize the technical variability. The acquired proteomics data were analyzed using Maxquant with 1% false discovery rate. A FASTA file containing whole human proteome, was used as the reference sequence for the search in the Andromeda database search tool. Additionally, another FASTA file containing 1187 proteins involved in the metabolism of endobiotics and xenobiotics was also searched to specifically identify the metabolic enzymes in both organs. The proteins were quantified using a generic label free quantification method (MaxLFQ) in Maxquant software. The metabolic enzymes common to both eye and liver S9 fractions were compared to determine the relative abundance values based on the resulting MaxLFQ intensities. The cut off for the differentially expressed proteins between the eye or liver was either <0.5 or >2. Results and Conclusion A total of 269 proteins (including 23 metabolic enzymes) were detected exclusively in the pooled eye S9, against 648 proteins in the liver S9 (including 174 metabolic enzymes), whereas 424 proteins (including 94 metabolic enzymes) were detected in both the organs. Among the common metabolic enzymes, 18 were predominant in the eye (Figure 1), 43 were predominant in the liver, while rest 33 were comparable in both samples. The major DMEs, viz., Cytochrome P450s, UDP-glucuronosyltransferases, and sulfotransferases, were not detected in the eye S9 fraction, instead isoforms of alcohol dehydrogenases, aldehyde dehydrogenases, carbonic anhydrases, aldo-keto reductases, esterases, epoxide hydrolases, and glutathione S-transferases were in abundance. This information bears great significance in gaining deeper insights on metabolic and bioactivation potential of both systemically as well as topically administered ophthalmic drugs as well as in the endobiotics metabolism within the eye. This investigation provides foundation for the subsequent targeted proteomic, genomic, and functional studies to explore the effects of sex, age, genotype and disease conditions across the populations.

Understanding metabolism related differences in ocular efficacy of MGV354

MGV354 was being developed as a novel ocular therapy for lowering of intraocular pressure, a key modifiable risk factor for glaucoma. MGV354 is an activator of soluble guanylate cyclase, an enzyme known to be involved in the regulation of IOP. MGV354 has been shown to robustly lower IOP over 24 h after a single topical ocular drop in rabbit and monkey pharmacology models. However, MGV354 failed to produce similar results in patients with ocular hypertension or open-angle glaucoma. With an objective of explaining the lack of efficacy in the clinic, we attempted to study whether human metabolism was significantly different from animal metabolism. The present study documents the investigation of metabolism of MGV354 in an effort to understand potential differences in biotransformation pathways of MGV354 in rabbits, monkeys, and humans. Overall twenty-six metabolites, formed via oxidative and conjugative pathways, were identified in vitro and in vivo. In vitro hepatic metabolism was qualitatively similar across species, with minor but distinct differences. There were no observable interspecies differences in the hepatic and ocular metabolism of MGV354. Although ocular metabolism was not as extensive as hepatic, the results do not explain the lack of efficacy of MGV354 in clinical studies.

Models and Approaches Describing the Metabolism, Transport, and Toxicity of Drugs Administered by the Ocular Route.

The eye is a complex organ with a series of anatomic barriers that provide protection from physical and chemical injury while maintaining homeostasis and function. The physiology of the eye is multifaceted, with dynamic flows and clearance mechanisms. This review highlights that in vitro ocular transport and metabolism models are confined by the availability of clinically relevant absorption, distribution, metabolism, and excretion (ADME) data. In vitro ocular transport models used for pharmacology and toxicity poorly predict ocular exposure. Although ocular cell lines cannot replicate in vivo conditions, these models can help rank-order new chemical entities in discovery. Historic ocular metabolism of small molecules was assumed to be inconsequential or assessed using authentic standards. While various in vitro models have been cited, no single system is perfect, and many must be used in combination. Several studies document the use of laboratory animals for the prediction of ocular pharmacokinetics in humans. This review focuses on the use of human-relevant and human-derived models which can be utilized in discovery and development to understand ocular disposition of new chemical entities. The benefits and caveats of each model are discussed. Furthermore, ADME case studies are summarized retrospectively and capture the ADME data collected for health authorities in the absence of definitive guidelines. Finally, we discuss the novel technologies and a hypothesis-driven ocular drug classification system to provide a holistic perspective on the ADME properties of drugs administered by the ocular route.

Investigation of Ocular Bioactivation Potential and the Role of Cytochrome P450 2D Enzymes in Rat.

Timolol is clinically administered topically (ocular) to reduce intraocular pressure and treat open-angle glaucoma. Ocular administration of timolol in low doses (0.5% w/v in the form of eye drops) has led to challenges for in vivo metabolite identification. An understanding of drug metabolism in the eye is important for clinical ocular therapeutics and potential drug candidates. We aimed to investigate the metabolism of timolol in rat ocular and liver S9 fractions, as well as rat ocular tissue and plasma following a 0.5% topical (ocular) dose of timolol. We explored the potential in vitro metabolic bioactivation in the eye/liver by conducting trapping studies for putative aldehyde and iminium ion intermediates that may arise from the morpholine functionality. Oxidative metabolism of timolol to its major metabolite (M4) in ocular S9 and recombinant rat cytochrome P450 (CYP) isoforms supports the possible role of rat ocular CYP2D2, 2D4, and/or 2D18. Observation of N-acetyl-timolol (M5) is suggestive that the ocular N-acetyltransferases may also play a larger role in ocular disposition of timolol, a previously unreported finding. This research is the first comprehensive report of in vitro ocular metabolism of timolol in rat. This study also indicates that in vitro hepatic metabolism is over-predictive of ocular metabolism following topically ocular dosed timolol. The research, herein, highlights the eye as an organ capable of first pass metabolism for topical drugs. Thus, new ophthalmologic considerations for studying and designing long term topical therapies in preclinical species are needed in drug discovery.

Topical Administration of Spironolactone-Loaded Nanomicelles Prevents Glucocorticoid-Induced Delayed Corneal Wound Healing in Rabbits.

The objective was to investigate whether mineralocorticoid receptor antagonism using a novel topical micellar formulation of spironolactone could prevent glucocorticoid-induced delayed corneal wound healing in New Zealand white rabbits. Spironolactone micelles (0.1%, w/v) with a mean number weighted diameter of 20 nm were prepared using a pegylated copolymer (mPEG-dihexPLA) and showed a preliminary stability of at least 12 months at 5 °C. Preclinical studies in New Zealand white rabbits demonstrated that the 0.1% spironolactone micellar formulation was well-tolerated since no reaction was observed in the cornea following multiple daily instillation over 5 days. As expected, the preclinical studies also confirmed that dexamethasone significantly delayed epithelial wound healing as compared to untreated control (percentage re-epithelialization after day 4: 84.6 ± 13.9% versus 99.5 ± 1.0% for the control, p < 0.05). However, the addition of the 0.1% spironolactone micellar formulation significantly improved the extent of re-epithelialization, countering the dexamethasone induced delayed wound healing with a percentage re-epithelialization that was statistically equivalent to the control (96.9 ± 7.3% versus 99.5 ± 1.0%, p > 0.05). The biodistribution study provided insight into the ocular metabolism of spironolactone and hence the relative contributions of the parent molecule and its two principal metabolites, 7α-thiomethylspironolactone and canrenone, to the observed pharmacological effects. Comparison of the efficacies of spironolactone and potassium canrenoate (a water-soluble precursor of canrenone) in overcoming the dexamethasone-induced delayed wound healing confirmed that the former had greater efficacy. The results pointed to the greater potency of 7α-thiomethylspironolactone over canrenone as a mineralocorticoid receptor antagonist, which explained its superior ability in countering the glucocorticoid-induced overactivation that was responsible for the delayed wound healing. In conclusion, the preliminary results supported the above-mentioned hypothesis suggesting that coadministration of mineralocorticoid receptor antagonists to patients under glucocorticoid therapy might prevent the deleterious effects of glucocorticoids on complex corneal wound healing processes.

Do We Need to Study Metabolism and Distribution in the Eye: Why, When, and Are We There Yet?

The liver is known to be the principal site of drug metabolism. Depending on the route of administration, especially in cases of topical and local delivery, evaluation of local drug metabolism in extrahepatic tissues is vital to assess fraction of the drug metabolized. This parameter becomes important from the point of view of drug availability or the contribution to overall clearance. Examples include fraction metabolized in the gut for oral drugs and contribution of pulmonary or renal clearance to total clearance of a drug. Diseases of the eye represent a rising unmet medical need and a number of therapeutics are currently being developed in the form of small molecules and biologics. Treatment of ocular diseases has expanded to explore various topical formulations and local short- and long-term therapies by ocular routes of administration. Until recently, metabolism in the eye for any species, including human, was not well documented, but this topic is gaining wide interest. Many in vitro–ex vivo models, each with separate pros and cons, are being used for studying ocular metabolism. This review is aimed at providing a perspective on the relevance and application of ocular metabolism, melanin binding, and the use of tissue- and cell-derived ocular models in discovery and preclinical development.

In vitro ocular metabolism and bioactivation of ketoconazole in rat, rabbit and human

Oral ketoconazole is clinically administered for treatment of severe cases for fungal keratitis. Pharmacodynamics and efficacy of oral and topical (ocular) ketoconazole have been explored in rabbit. However, metabolism of ketoconazole in the eye in any species is not well explored in any preclinical species or human. An understanding of ocular drug metabolism in the eye is crucial for ocular therapeutics to facilitate the risk assessment and development of potential drug candidates for the clinic. We aimed to investigate the metabolism of ketoconazole in rat, rabbit and human ocular S9 fractions. Metabolism in liver S9 fractions was also studied for a direct comparison. Eleven putative metabolites were identified in the in vitro incubations. Of these metabolites, six were present in rat ocular S9 whereas eight were present in rabbit and human ocular matrices. Metabolic pathways in rabbit and human ocular fractions suggested the formation of reactive intermediates in rabbit and human liver and ocular S9 incubations, which was confirmed with trapping studies. Herein, we report eight human ocular metabolites of ketoconazole for the first time. To the best of our knowledge, this is the first report of ocular metabolic pathways and ocular bioactivation of ketoconazole in preclinical species and human.

Ocular Metabolism of Levobunolol: Historic and Emerging Metabolic Pathways

Although ocular transport and delivery have been well studied, metabolism in the eye is not well documented, even for clinically available medications such as levobunolol, a potent and nonselective β-adrenergic receptor antagonist. Recently, we reported an in vitro methodology that could be used to evaluate ocular metabolism across preclinical species and humans. The current investigation provides detailed in vitro ocular and liver metabolism of levobunolol in rat, rabbit, and human S9 fractions, including the formation of equipotent active metabolite, dihydrolevobunolol, with the help of high-resolution mass spectrometry. 11 of the 16 metabolites of levobunolol identified herein, including a direct acetyl conjugate of levobunolol observed in all ocular and liver fractions, have not been reported in the literature. The study documents the identification of six human ocular metabolites that have never been reported. The current investigation presents evidence for ocular and hepatic metabolism of levobunolol via non-cytochrome P450 pathways, which have not been comprehensively investigated to date. Our results indicated that rat liver S9 and human ocular S9 fractions formed the most metabolites. Furthermore, liver was a poor in vitro surrogate for eye, and rat and rabbit were poor surrogates for human in terms of the rate and extent of levobunolol metabolism.

Assessment of Active Metabolites of Levobunolol and Betaxolol in Rat, Rabbit and Human Ocular and Liver S9 Fractions

Little is known about ocular metabolism and formation of pharmacologically active metabolites for drugs dosed topically to the eye. We devised a simple in vitro approach coupled with high resolution mass spectrometry to measure the rate and extent of ocular metabolism for comparison with liver. Levobunolol and betaxolol are antagonists of β‐adrenergic receptors and have been clinically utilized for treatment of primary open‐angle glaucoma and/or ocular hypertension. Levobunolol has been reported to be metabolized to an equipotent active metabolite, dihydrolevobunolol, in plasma and urine of mice, rat, dog, and human. Hydroxybetaxolol, an active metabolite of betaxolol, has been reported in the liver. We aimed to understand whether the eye has functional metabolic activity and to understand the extent of formation of two historically reported in vivo active metabolites, one each for levobunolol and betaxolol, across rat (R), rabbit (Rbt) and human (H) ocular S9 (OS9) fractions and liver S9 (LS9) fractions. Based on high resolution mass spectrometry M11 was identified as the active dihydroxylevobunolol while M2 was identified as the active hydroxybetaxolol. The in vitro data shows that betaxolol's M2 was formed in the eye across preclinical species and human. M2 pharmacological activity for antagonism toward β1‐ or β2‐receptors has not been assessed to date. This is the first report of hydroxybetaxolol being formed in the eye. Results from levobunolol and betaxolol metabolism studies point toward species differences in conversion of levobunolol and betaxolol to their respective active metabolites and strongly indicate that LS9 fractions are a poor surrogate for assessment of active metabolites formed in the eye.

An in vitro approach to investigate ocular metabolism of a topical, selective β1-adrenergic blocking agent, betaxolol

1. Topical glaucoma treatments have often been limited by poor absorption and bioavailability. Betaxolol, a selective β1-blocker, has been well studied for its pharmacokinetics and disposition. Limited ocular, betaxolol metabolism data is available despite a growing number of novel ocular treatments.2. In vitro ocular fractions indicated the formation of an active metabolite, across rat, rabbit and human, which was only observed historically in the liver.3. Ocular metabolic profiles of preclinical toxicology species, rat and rabbit, were not predictive of human in vitro ocular data. M1 was specific to human and only captured by the liver data.4. Liver S9 over predicted the extent of ocular metabolism compared to ocular fractions. Rabbit liver S9 fractions demonstrated extensive glucuronidation and higher parent turn-over in 1 h as compared to other matrices.5. This research assesses in vitro species and organ differences across preclinical species and human. The complex data set highlights the need for an in vitro ocular system to explore poorly documented ocular metabolism.

FcRn mediated IgG transport by retinal pigment epithelium cells

Background The neonatal Fc receptor (FcRn) binds immunoglobulin G (IgG), protects it from degradation and can transport IgG from apical to basolateral side of epithelial cells [1]. Previously, we showed that human retinal pigment epithelial (RPE) cells express FcRn and that, in contrast to non-ocular cells, TNF-a downregulates FcRn expression in RPE cells [2]. We speculated that FcRn in RPE plays a pivotal role in ocular IgG metabolism. The aim of this study was to develop a method to investigate whether RPE cells transport IgG molecules.

Glaucoma and ocular blood flow: an anatomical perspective

Open-angle glaucoma (OAG) is a chronic progressive optic neuropathy that is increasing in prevalence worldwide. Currently, intraocular pressure is the only known modifiable risk factor. With lowering of intraocular pressure, the proportion of individuals who experience progression of visual field defects is reduced but continues to occur in some individuals. Many other risk factors have been identified, including decreased ocular perfusion pressure and decreased ocular blood flow. Various imaging methodologies have shown an association between OAG and altered blood flow in the various circulations: retrobulbar, retinal, optic nerve head and choroidal. In addition, different morphological alterations have been found to be associated with OAG. This review will cover the evidence that supports the association between altered ocular blood flow and glaucoma. Furthermore, it serves to describe the future methodologies that will assess ocular metabolism, which will strive to move the field closer to definitively understanding the effect of vascular changes on OAG.

Frinoderma secundario a déficit de vitamina A en un paciente con derivación biliopancreática

Biliopancreatic diversion (BPD) is a malabsorptive bariatric procedure can lead to the development of several nutritional complications, including fat-soluble vitamins deficiencies. Routine supplementation with vitamins and trace elements and a close follow-up long-term can prevent these nutritional risks. Vitamin A participates in ocular metabolism, epithelial differentiation, growth, and embryogenesis. Have been described several cases of ophthalmological and fetal complications associated with vitamin A deficiency in patients who have undergone BPD. Few information exists in literature about dermatologic manifestations that may occur in these patients. Phrynoderma is a type of follicular hyperkeratosis located on the extensor surfaces of the extremities whose main cause is vitamin A deficiency. We report an exceptional case of severe cutaneous and ocular complications in a patient who had undergone BPD with poor adherence to treatment and postoperative follow-up. Our patient presented simultaneously the characteristic skin lesions of phrynoderma with nytalopia and xerophthalmia in a setting of low serum levels of vitamin A. Treatment with high doses vitamin A obtained the resolution of both processes. We review and discuss the relationship between phrynoderma, malnutrition and vitamin A deficiency.