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Summary: Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure. This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA. Inhibition of UTX/KDM6B enzymatic activity condenses chromatin structure, prevents MRTF-A binding, blocks activation of the pro-fibrotic transcriptome, and results in an inhibition of fibrosis in lens and lung fibrosis models. Our work reveals UTX/KDM6B as central coordinators of fibrosis, highlighting the potential to target its demethylase activity to prevent organ fibrosis.

Visual loss in systemic lupus erythematosus (SLE) due to autoimmune retinopathy (AIR) is rare and easily misdiagnosed as hydroxychloroquine retinopathy. We report the rare clinical presentation of severe visual loss in a patient with SLE due to nonparaneoplastic AIR as differentiated from hydroxychloroquine toxicity. A 70-year-old female diagnosed and treated for lupus for 17 years and had been taking hydroxychloroquine for 15 years. Over the past 2 years, she developed progressive peripheral visual loss oculus uterque which rapidly advanced in the latter 6 months. Hydroxychloroquine toxicity was initially suspected, but diagnostic testing revealed a retinal degeneration. Antiretinal autoantibody testing using Western blot analysis revealed autoantibodies against 44-kDa, 46-kDa (anti-enolase), and 68-kDa proteins. Visual acuity improved in the first 6 months of treatment with mycophenolate mofetil. Our case suggests that AIR should be considered in the differential diagnosis of rapid, severe visual loss in patients with hydroxychloroquine treatment.

Introduction: The etiologies of congenital and developmental cataracts are diverse. Most are not syndromic and have no identifiable cause, thus creating a diagnostic dilemma. We investigated the utility of chromosomal microarray in identifying the etiology of isolated childhood cataracts. Methods: Patients with congenital or developmental cataracts without other associated abnormalities received a single-nucleotide polymorphism (SNP) microarray. copy number variations (CNV) and regions of homozygosity (ROH) were compared with previous literature reports and analyzed for candidate genes to assess pathogenicity. Results: We enrolled 37 patients. The mean age of the patient population was 10.98 years old. Nineteen patients (51.4%) had bilateral cataract. Positive family history was found in 11 patients (29.7%). Eighteen patients (48.7%) had a variant on microarray: 10 (27%) with CNV, 5 (13.5%) with ROH, and 3 patients (8.1%) with both CNV and homozygosity. In five patients (13.5%), we found a potentially causative cataract gene within an ROH. Discussion: There is a high rate of notable findings among the CNV and ROH detected. Three patients were homozygous in a region known to have a cataract gene suggesting a possible autosomal recessive disease. In those with CNV, segregation would help to affirm the pathogenicity of these regions and may lead to the identification of new genes. Conclusion: SNP microarray had a surprisingly high rate of notable findings in patients with isolated cataract and may reveal the opportunities for genetic counseling, lead to discovering new cataract genes and identify additional affected genes that could lead to other clinical abnormalities.

In this communication, we report the case of a four year old boy who presented with reduced vision in the right eye. He had visual acuity of light perception right eye and 6/12 in the left eye and anterior segment examination was normal. Fundus examination of the right eye showed a falciform retinal fold extending from the optic nerve temporally involving the entire retina with exudates within the falciform fold and dense pigmentation peripherally. The left eye showed mild macular temporal dragging of the vessels and 360° of peripheral laser scars. In addition he also had some characteristic systemic features such as developmental delay, obesity, dysmorphic facies and tapered fingers. Using this case as an example, we present a systematic, logical approach to a patient with a possible genetic disorder. The growing field of ocular genetics now allows for improved diagnosis using step-wise cost efficient testing as demonstrated herein.

Organophosphates have rarely been reported to cause various ocular sequelae including retinal degeneration. Retinal manifestations have been rarely reported and poorly characterized. We describe a case of a 76-year-old man with vision loss beginning in his 20s due to acute on chronic exposure to dimethoate, an organophosphate. He presented with bilateral geographic macular atrophy and midperipheral pigmentary clumping which we characterized by dilated fundoscopic examination, optical coherence tomography, and fundus autofluorescence.

The eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails), nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in the fundus of a female carrier of ocular albinism. Basic concepts of genetics and their application to clinical ophthalmological practice are important not only in making a precise diagnosis and appropriate referral, but also in management and genetic counseling.

The purpose of this study is to describe transient macular cysts in an infant and correlate their occurrence with normal development events. A newborn Caucasian girl presented with a protruding corneal mass in her left eye at birth. She underwent a complete ophthalmic examination. A keratinized staphylomatous malformation involving the entire cornea and precluding further visualization of the anterior and posterior segment was observed in the left eye. Spectral domain optical coherence tomography (SD-OCT) of the right eye performed when the child was approximately 6-week-old had revealed an unexpected finding of macular cysts involving the inner nuclear and outer retinal layers. Corneal transplant in the left eye was performed a month later. Ocular examination under anesthesia just prior to surgery revealed normal intraocular pressure, anterior segment and retina in the right eye. SD-OCT was normal in both eyes and showed complete resolution of the cysts in the right eye. The patient had not been on any medications at that time. Although clinical retinal examination might be unremarkable, SD-OCT may reveal cystic spaces in the macula. In the absence of conditions known to be associated with macular edema, transient macular cysts may arise due to a developmental incompetence of the blood-retinal barrier or may represent transient spaces created during normal migration of retinal cells. Further study is warranted to delineate the entity of transient macular cysts in infancy.

The anterior segment dysgeneses are a broad group of heterogeneous disorders characterized by developmental abnormalities of the anterior segment of the eye, including primary congenital aphakia, Peters sequence, aniridia, and Axenfeld–Rieger spectrum. These conditions can have overlapping phenotypes and both genotypic and phenotypic heterogeneity. This article provides a strategy for both phenotyping and then genotyping using a targeted stepwise approach.