Development and validation of a method to generate phenol red thread tests.

PURPOSE: The aim of this study was to develop and validate a method to generate phenol red thread tests (PRTT) due to the lack of availability of commercial PRTT. METHODS: White cotton thread was dyed with phenol red (pH indicator) for 48 hours, dried, cut, and sterilized. To validate its wicking ability, the thread was inserted into solutions of varying pH, flanking the pH of healthy tears, for different time intervals. To assess its diagnostic utility, PRTTs were performed in vivo on wildtype and a murine model of evaporative dry eye, acyl-coA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mice. RESULTS: Two batches of PRTT were produced that had a similar appearance and function to the commercial product. In vitro testing revealed no significant differences in the wicking kinetics at any time point across the pH solutions for batch 1 and only one difference for batch 2 (pH 7.4 vs 7.8 at 5 s, P=0.029). When comparing both batches, similar wicking kinetics were found with only two significant differences identified (pH 7.6 at 40 s and pH 7.8 at 35 s, P<0.01). In vivo, our PRTT yielded similar measurements to the commercial PRTT in wildtype and Awat2 KO mice and detected a significant increase in aqueous tear volume in the Awat2 KO mice (commercial: P=0.015, our PRTT: P=0.002). CONCLUSION: Our method provides a reproducible diagnostic test that performs similarly to its commercial counterpart in a relevant dry eye model indicating that it can serve as a valid and reliable replacement.

The effects of age and dysfunction on meibomian gland population dynamics.

PURPOSE: While meibomian gland dysfunction (MGD) is widely recognized as a major cause of evaporative dry eye disease, little is known about normal gland differentiation and lipid synthesis or the mechanism underlying gland atrophy and abnormal lipid secretion. The purpose of this study was to use single-cell and spatial transcriptomics to probe changes in cell composition, differentiation, and gene expression associated with two murine models of MGD: age-related gland atrophy in wild-type mice and altered meibum quality in acyl-CoA wax alcohol acyltransferase 2 (Awat2) knockout (KO) mice. METHODS: Young (6 month) and old (22 month) wild type, C57Bl/6 mice and young (3 month) and old (13 month) Awat2 KO mice were used in these studies. For single-cell analysis, the tarsal plate was dissected from the upper and lower eyelids, and single cells isolated and submitted to the UCI Genomic Core, while for the spatial analysis frozen tissue sections were shipped to Resolve Biosciences on dry ice and sections probed in duplicate using a meibomian gland specific, 100 gene Molecular Chartography panel. RESULTS: Analysis of gene expression patterns identified the stratified expression of lipogenic genes during meibocyte differentiation, which may control the progressive synthesis of meibum lipids; an age-related decrease in meibocytes; and increased immune cell infiltration. Additionally, we detected unique immune cell populations in the Awat2 KO mouse suggesting activation of psoriasis-like, inflammatory pathways perhaps caused by ductal dilation and hyperplasia. CONCLUSION: Together these findings support novel mechanism controlling gland function and dysfunction.

Biomechanic, proteomic and miRNA transcriptional changes in the trabecular meshwork of primates injected with intravitreal triamcinolone.

Although biomechanical changes of the trabecular meshwork (TM) are important to the pathogenesis of glucocorticoids-induced ocular hypertension (GC-OHT), there is a knowledge gap in the underlying molecular mechanisms of the development of it. In this study, we performed intravitreal triamcinolone injection (IVTA) in one eye of 3 rhesus macaques. Following IVTA, we assessed TM stiffness using atomic force microscopy and investigated changes in proteomic and miRNA expression profiles. One of 3 macaques developed GC-OHT with a difference in intraocular pressure of 4.2 mmHg and a stiffer TM with a mean increase in elastic moduli of 0.60 kPa versus the non-injected control eye. In the IVTA-treated eyes, proteins associated with extracellular matrix remodeling, cytoskeletal rearrangement, and mitochondrial oxidoreductation were significantly upregulated. The significantly upregulated miR-29b and downregulated miR-335-5p post-IVTA supported the role of oxidative stress and mitophagy in the GC-mediated biomechanical changes in TM, respectively. The significant upregulation of miR-15/16 cluster post-IVTA may indicate a resultant TM cell apoptosis contributing to the increase in outflow resistance. Despite the small sample size, these results expand our knowledge of GC-mediated responses in the TM and furthermore, may help explain steroid responsiveness in clinical settings.

Topical netarsudil for the treatment of primary corneal endothelial degeneration in dogs.

This study evaluated the tolerability and efficacy of the topical rho-kinase inhibitor netarsudil for canine primary corneal endothelial degeneration (PCED). Twenty-six eyes of 21 client-owned dogs with PCED were enrolled in a prospective, randomized, vehicle control clinical trial and received topical netarsudil 0.02% (Rhopressa®) or vehicle control twice daily (BID) for the first 4 months. Then, all patients received netarsudil for the next 4 or 8 months. Complete ophthalmic examination, ultrasonic pachymetry, Fourier-domain optical coherence tomography, and in vivo confocal microscopy were performed at baseline and 1, 2, 4, 6, 8 and 12 months. Effect of netarsudil on central corneal thickness (CCT), percentage of cornea with edema, and endothelial cell density (ECD) were evaluated by repeated measures ANOVA. Kaplan-Meier curves and log-rank test were used to compare corneal edema and clinical progression of eyes in netarsudil versus vehicle control groups. All dogs developed conjunctival hyperemia in at least one eye while receiving netarsudil. Unilateral transient reticulated intraepithelial bullae and stromal hemorrhage were observed respectively in 2 dogs in the netarsudil group. Two dogs showed persistently decreased tear production while receiving netarsudil, requiring topical immunomodulatory treatment. No significant differences in CCT, ECD, corneal edema or clinical progression were observed between netarsudil or vehicle treated eyes. When comparing efficacy of topical netarsudil BID and topical ripasudil 0.4% administered four times daily from our previous study, dogs receiving ripasudil had significantly less progression than those receiving netarsudil.

Engineered Dual Antioxidant Enzyme Complexes Targeting ICAM-1 on Brain Endothelium Reduce Brain Injury-Associated Neuroinflammation.

The neuroinflammatory cascade triggered by traumatic brain injury (TBI) represents a clinically important point for therapeutic intervention. Neuroinflammation generates oxidative stress in the form of high-energy reactive oxygen and nitrogen species, which are key mediators of TBI pathology. The role of the blood-brain barrier (BBB) is essential for proper neuronal function and is vulnerable to oxidative stress. Results herein explore the notion that attenuating oxidative stress at the vasculature after TBI may result in improved BBB integrity and neuroprotection. Utilizing amino-chemistry, a biological construct (designated "dual conjugate" for short) was generated by covalently binding two antioxidant enzymes (superoxide dismutase 1 (SOD-1) and catalase (CAT)) to antibodies specific for ICAM-1. Bioengineering of the conjugate preserved its targeting and enzymatic functions, as evaluated by real-time bioenergetic measurements (via the Seahorse-XF platform), in brain endothelial cells exposed to increasing concentrations of hydrogen peroxide or a superoxide anion donor. Results showed that the dual conjugate effectively mitigated the mitochondrial stress due to oxidative damage. Furthermore, dual conjugate administration also improved BBB and endothelial protection under oxidative insult in an in vitro model of TBI utilizing a software-controlled stretching device that induces a 20% in mechanical strain on the endothelial cells. Additionally, the dual conjugate was also effective in reducing indices of neuroinflammation in a controlled cortical impact (CCI)-TBI animal model. Thus, these studies provide proof of concept that targeted dual antioxidant biologicals may offer a means to regulate oxidative stress-associated cellular damage during neurotrauma.

Squishy matters - Corneal mechanobiology in health and disease.

The cornea, as a dynamic and responsive tissue, constantly interacts with mechanical forces in order to maintain its structural integrity, barrier function, transparency and refractive power. Cells within the cornea sense and respond to various mechanical forces that fundamentally regulate their morphology and fate in development, homeostasis and pathophysiology. Corneal cells also dynamically regulate their extracellular matrix (ECM) with ensuing cell-ECM crosstalk as the matrix serves as a dynamic signaling reservoir providing biophysical and biochemical cues to corneal cells. Here we provide an overview of mechanotransduction signaling pathways then delve into the recent advances in corneal mechanobiology, focusing on the interplay between mechanical forces and responses of the corneal epithelial, stromal, and endothelial cells. We also identify species-specific differences in corneal biomechanics and mechanotransduction to facilitate identification of optimal animal models to study corneal wound healing, disease, and novel therapeutic interventions. Finally, we identify key knowledge gaps and therapeutic opportunities in corneal mechanobiology that are pressing for the research community to address especially pertinent within the domains of limbal stem cell deficiency, keratoconus and Fuchs' endothelial corneal dystrophy. By furthering our understanding corneal mechanobiology, we can contextualize discoveries regarding corneal diseases as well as innovative treatments for them.

Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis.

Purpose: This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1. Results: Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%). Conclusions: AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up. Translational Relevance: This systematic review will help to inform and guide future clinical trials.

Oculosystemic pneumocystosis in 2 sibling Chihuahuas.

Sibling female and male Chihuahuas were evaluated for a 9-month history of tachypnea that failed to respond to fenbendazole, doxycycline, amoxicillin-clavulanate, and prednisone. Physical examination identified tachypnea, hyperpnea, and harsh bronchovesicular lung sounds. Fundic examination disclosed diffuse chorioretinitis, manifested as multifocal chorioretinal granulomas in the female dog and occasional chorioretinal scars in the male dog. Thoracic radiographs indicated moderate to severe interstitial to broncho-interstitial infiltrates in both dogs. Serum and urine antigen and antibody testing in the female dog failed to identify infectious agents, but cytologic assessment of hepatic lymph node, liver, and splenic aspirates identified Pneumocystis trophozoites. Infection was confirmed in both dogs by 28S rRNA PCR sequencing from multiple tissue samples. The female dog responded well to trimethoprim-sulfamethoxazole, but the male dog was euthanized because of liver failure, presumably related to antimicrobial treatment.

Threonine functionalized colloidal cadmium sulfide (CdS) quantum dots: The role of solvent and counterion in ligand induced chiroptical properties.

The functionalization of semiconductor nanocrystals, quantum dots (QDs), with small organic molecules has been studied extensively to gain better knowledge on how to tune the electronic, optical and chiroptical properties of QDs. Chiral QDs have progressively emerged as key materials in a vast range of applications including biosensing and biorecognition, imaging, asymmetric catalysis, optoelectronic devices, and spintronics. To engage the full potential of the unique properties of chiral nanomaterials and be able to prepare them with tailorable chiroptical characteristics, it is essential to understand how chirality is rendered from chiral molecular ligands at the surface of nanocrystals to the electronic states of QDs. Using a series of polar protic and aprotic solvents together with ammonium (NH4+), tetramethylammonium (TMA+), and tetrabutylammonium (TBA+) countercations in the preparation of threonine-functionalized cadmium sulfide (Thr-CdS) QDs by phase transfer ligand exchange approach, we demonstrated the significance of the role both the solvent and the countercations play in the transfer of chirality from chiral molecular ligand to achiral semiconductor QDs as apparent by the modulations of the signatures and anisotropy of the circular dichroism (CD) spectra. Moreover, we have utilized tetrabutylammonium countercation to successfully synthesize chiral QDs in nonpolar cyclohexane solvent for the first time. This study provides further insights into the origin of the ligand induced chirality of colloidal nanomaterials and facilitates the synthesis of tailormade chiral QDs.

Mice Deficient in TAZ (Wwtr1) Demonstrate Clinical Features of Late-Onset Fuchs' Endothelial Corneal Dystrophy.

Purpose: We sought to define the role of Wwtr1 in murine ocular structure and function and determine the role of mechanotransduction in Fuchs' endothelial corneal dystrophy (FECD), with emphasis on interactions between corneal endothelial cells (CEnCs) and Descemet's membrane (DM). Methods: A Wwtr1 deficient mouse colony was established, and advanced ocular imaging, atomic force microscope (AFM), and histology/immunofluorescence were performed. Corneal endothelial wound healing was assessed using cryoinjury and phototherapeutic keratectomy in Wwtr1 deficient mice. Expression of WWTR1/TAZ was determined in the corneal endothelium from normal and FECD-affected patients; WWTR1 was screened for coding sequence variants in this FECD cohort. Results: Mice deficient in Wwtr1 had reduced CEnC density, abnormal CEnC morphology, softer DM, and thinner corneas versus wildtype controls by 2 months of age. Additionally, CEnCs had altered expression and localization of Na/K-ATPase and ZO-1. Further, Wwtr1 deficient mice had impaired CEnC wound healing. The WWTR1 transcript was highly expressed in healthy human CEnCs comparable to other genes implicated in FECD pathogenesis. Although WWTR1 mRNA expression was comparable between healthy and FECD-affected patients, WWTR1/TAZ protein concentrations were higher and localized to the nucleus surrounding guttae. No genetic associations were found in WWTR1 and FECD in a patient cohort compared to controls. Conclusions: There are common phenotypic abnormalities seen between Wwtr1 deficient and FECD-affected patients, suggesting that Wwtr1 deficient mice could function as a murine model of late-onset FECD. Despite the lack of a genetic association between FECD and WWTR1, aberrant WWTR1/TAZ protein subcellular localization and degradation may play critical roles in the pathogenesis of FECD.

COVID-19 as a polymorphic inflammatory spectrum of diseases: a review with focus on the brain.

There appear to be huge variations and aberrations in the reported data in COVID-19 2 years now into the pandemic. Conflicting data exist at almost every level and also in the reported epidemiological statistics across different regions. It is becoming clear that COVID-19 is a polymorphic inflammatory spectrum of diseases, and there is a wide range of inflammation-related pathology and symptoms in those infected with the virus. The host's inflammatory response to COVID-19 appears to be determined by genetics, age, immune status, health status and stage of disease. The interplay of these factors may decide the magnitude, duration, types of pathology, symptoms and prognosis in the spectrum of COVID-19 disorders, and whether neuropsychiatric disorders continue to be significant. Early and successful management of inflammation reduces morbidity and mortality in all stages of COVID-19.

Development of a value-based care and population health internship for student pharmacists.

INTRODUCTION: Pharmacists assist in achieving desired outcomes and reducing costs of care within newer value-based payment models. The purpose of this article is to describe a summer internship for first- and second-year student pharmacists to gain exposure to value-based care. METHODS: University Health Network is a clinically integrated health network and accountable care organization in East Tennessee. Two student interns completed consecutive seven-week programs alongside clinical pharmacist specialists in the primary care settings of the network. Program requirements included direct patient care for chronic disease state management, topic discussions, formal writing assignments and presentations, and a quality improvement project. Student perception of internship activities was measured using a Likert type survey and free response questionnaire. RESULTS: Student interns responded positively to program requirements with feelings of enhanced preparedness for advanced pharmacy practice experiences and post-graduate residency positions. Additionally, interns perceived themselves as more competitive for post-graduate positions having completed the internship. CONCLUSIONS: As the US continues to move toward value-based payment models, student pharmacists must be well prepared to contribute to quality and population health initiatives. Student pharmacists benefit from an internship in a clinically integrated health network by gaining an improved understanding of the future of United States healthcare, an expanded clinical skillset, experience in demonstrating a pharmacist's value to the healthcare team, and the ability to overcome barriers to pharmacy services. A pharmacy internship within a clinically integrated health network may help prepare students to successfully contribute to value-based models of healthcare.

A comparative review of evaporative dry eye disease and meibomian gland dysfunction in dogs and humans.

Dry eye disease is a complex ophthalmic disorder that consists of two main subtypes, aqueous deficient dry eye (ADDE) and evaporative dry eye disease (EDED). Due to the complex underlying physiology, human dry eye disease can be difficult to model in laboratory animal species. Thus, the identification and characterization of a spontaneous large animal model of dry eye disease is desirable. Dogs have been described as an ideal spontaneous model of ADDE due to the similar pathophysiology between dogs and humans. Recently, EDED and meibomian gland dysfunction (MGD) have been increasingly recognized and reported in dogs. These reports on EDED and MGD in dogs have identified similarities in pathophysiology, clinical presentations, and diagnostic parameters to humans with the comparable disorders. Additionally, the tests that are used to diagnose EDED and MGD in humans are more easily applicable to dogs than to laboratory species due to the comparable globe sizes between dogs and humans. The reported response of dogs to EDED and MGD therapies are similar to humans, suggesting that they would be a valuable preclinical model for the development of additional therapeutics. Further research and clinical awareness of EDED and MGD in dogs would increase their ability to be utilized as a preclinical model, improving the positive predictive value of therapeutics for EDED and MGD in both humans and dogs.

Effect of graphene-based nanomaterials on corneal wound healing in vitro.

Graphene-based nanomaterials (GBNs) are widely used due to their chemical and physical properties for multiple commercial and environmental applications. From an occupational health perspective, there is concern regarding the effects of inhalation on the respiratory system, and many studies have been conducted to study inhalation impacts on lung. Similar to the respiratory system, the eyes may also be exposed to GBNs and thus impacted. In this study, immortalized human corneal epithelial (hTCEpi) cells and rabbit corneal fibroblasts (RCFs) were used to investigate the toxicity of eight types of GBN: graphene oxide (GO; 400 nm), GO (1 µm), partially reduced graphene oxide (PRGO; 400 nm), reduced graphene oxide (RGO; 400 nm), RGO (2 µm), graphene (110 nm), graphene (140 nm), and graphene (1 µm). We next examined the effects of these GBNs on hTCEpi cell migration. We also determined whether the expression of α-smooth muscle actin (αSMA), a myofibroblast marker, is altered by the GBNs using RCFs. We found that RGO (400 nm) and RGO (2 µm) were highly toxic to hTCEPi cells and RCFs meanwhile, PRGO (400 nm) was toxic only to hTCEpi cells. In addition, PRGO (400 nm), RGO (400 nm), and RGO (2 µm) inhibited hTCEpi cell migration and significantly increased αSMA mRNA expression. Further study in vivo is required to determine if RGO nanomaterials delay corneal epithelial healing and induce scar formation.

Identification of putative orthologs of clinically relevant antimicrobial peptides in the equine ocular surface and amniotic membrane.

OBJECTIVES: This study aimed to define the antimicrobial peptide (AMP) expression pattern of the equine ocular surface and amniotic membrane using a targeted qPCR approach and 3'Tag-sequencing. It will serve as a reference for future studies of ocular surface innate immunity and amniotic membrane therapies. PROCEDURES: A targeted qPCR approach was used to investigate the presence of orthologs for three of the most highly expressed beta-defensins (DEFB1, DEFB4B, and DEFB103A) of the human ocular surface and amniotic membrane in equine corneal epithelium, conjunctiva, and amniotic membrane. 3'Tag-sequencing was performed on RNA from one sample of corneal epithelium, conjunctiva, and amniotic membrane to further characterize their AMP expression. RESULTS: Equine corneal epithelium, conjunctiva, and amniotic membrane expressed DEFB1, DEFB4B, and DEFB103A. DEFB103A was expressed at the highest amounts in corneal epithelium, while DEFB4B was most highly expressed in conjunctiva and amniotic membrane. 3'Tag-sequencing from all three tissues confirmed these findings and identified expression of five additional beta-defensins, 11 alpha-defensins and two cathelicidins, with the alpha-defensins showing higher normalized read counts than the beta-defensins. CONCLUSIONS: This study identified AMP expression in the equine cornea and conjunctiva, suggesting that they play a key role in the protection of the equine eye, similar to the human ocular surface. We also determined that equine amniotic membrane expresses a substantial number of AMPs suggesting it could potentiate an antimicrobial effect as a corneal graft material. Future studies will focus on defining the antimicrobial activity of these AMPs and determining their role in microbial keratitis.

A review of diagnostic tests for qualitative and quantitative tear film deficiency in dogs.

Dry eye disease (DED) is a complex multifactorial condition caused by loss of ocular surface homeostasis from quantitative and/or qualitative tear film deficiency. Schirmer tear test (STT) is often the only diagnostic test used to assess for DED in veterinary practice. STT is invaluable in the diagnosis and monitoring of quantitative tear film deficiency (i.e., keratoconjunctivitis sicca); however, it is not sufficient to optimize therapy and fully recognize other contributing factors for the disturbance in ocular surface homeostasis. The present work reviews diagnostic tests for assessing aqueous tear production in veterinary medicine, as well as the quality of tears, corneal epithelial barrier integrity, and the lacrimal functional unit.

Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis.

Introduction: Equine recurrent uveitis (ERU), an immune mediated disease characterized by repeated episodes of intra-ocular inflammation, affects 25% of horses in the USA and is the most common cause of glaucoma, cataracts, and blindness. Mesenchymal stromal cells (MSCs) have immunomodulatory properties, which are upregulated by preconditioning with toll-like receptor agonists. The objective was to evaluate safety and migration of TLR-3 agonist polyinosinic, polycytidylic acid (pIC)-activated MSCs injected subconjunctivally in healthy horses prior to clinical application in horses with ERU. We hypothesized that activated allogeneic MSCs injected subconjunctivally would not induce ocular or systemic inflammation and would remain in the conjunctiva for >14 days. Methods: Bulbar subconjunctiva of two horses was injected with 10 × 106 pIC-activated (10 µg/mL, 2 h) GFP-labeled MSCs from one donor three times at two-week intervals. Vehicle (saline) control was injected in the contralateral conjunctiva. Horses received physical and ophthalmic exams [slit lamp biomicroscopy, rebound tonometry, fundic examination, and semiquantitative preclinical ocular toxicology scoring (SPOTS)] every 1-3 days. Systemic inflammation was assessed via CBC, fibrinogen, and serum amyloid A (SAA). Horses were euthanized 14 days following final injection. Full necropsy and histopathology were performed to examine ocular tissues and 36 systemic organs for MSC presence via IVIS Spectrum. Anti-GFP immunohistochemistry was performed on ocular tissues. Results: No change in physical examinations was noted. Bloodwork revealed fibrinogen 100-300 mg/dL (ref 100-400) and SAA 0-25 µg/mL (ref 0-20). Ocular effects of the subjconjucntival injection were similar between MSC and control eyes on SPOTS grading system, with conjunctival hypermia, chemosis and ocular discharge noted bilaterally, which improved without intervention within 14 days. All other ocular parameters were unaffected throughout the study. Necropsy and histopathology revealed no evidence of systemic inflammation. Ocular histopathology was similar between MSC and control eyes. Fluorescent imaging analysis did not locate MSCs. Immunohistochemistry did not identify intact MSCs in the conjunctiva, but GFP-labeled cellular components were present in conjunctival phagocytic cells. Discussion: Allogeneic pIC-activated conjunctival MSC injections were well tolerated. GFP-labeled tracking identified MSC components phagocytosed by immune cells subconjunctivally. This preliminary safety and tracking information is critical towards advancing immune conditioned cellular therapies to clinical trials in horses.

Ocular morphologic traits in the American Cocker Spaniel may confer primary angle closure glaucoma susceptibility.

Acute primary angle closure glaucoma is a potentially blinding ophthalmic emergency requiring prompt treatment to lower the elevated intraocular pressure in humans and dogs. The PACG in most of canine breeds is epidemiologically similar to humans with older and female patients overrepresented with the condition. The American Cocker Spaniel (ACS) is among the most common breeds observed with PACG development in dogs. This study initially sought to identify genetic risk factors to explain the high prevalence of PACG in ACSs by using a case-control breed-matched genome-wide association study. However, the GWAS failed to identify candidate loci associated with PACG in this breed. This study then assessed intrinsic ocular morphologic traits that may relate to PACG susceptibility in this breed. Normal ACSs without glaucoma have a crowded anterior ocular segment and narrow iridocorneal angle and ciliary cleft, which is consistent with anatomical risk factors identified in humans. The ACSs showed unique features consisting of posterior bowing of iris and longer iridolenticular contact, which mirrors reverse pupillary block and pigment dispersion syndrome in humans. The ACS could hold potential to serve as an animal model of naturally occurring PACG in humans.