Ilya Leskov

The Gain of Rod Phototransduction: Reconciliation of Biochemical and Electrophysiological Measurements

We have resolved a central and long-standing paradox in understanding the amplification of rod phototransduction by making direct measurements of the gains of the underlying enzymatic amplifiers. We find that under optimized conditions a single photoisomerized rhodopsin activates transducin molecules and phosphodiesterase (PDE) catalytic subunits at rates of 120-150/s, much lower than indirect estimates from light-scattering experiments. Further, we measure the Michaelis constant, Km, of the rod PDE activated by transducin to be 10 microM, at least 10-fold lower than published estimates. Thus, the gain of cGMP hydrolysis (determined by kcat/Km) is at least 10-fold higher than reported in the literature. Accordingly, our results now provide a quantitative account of the overall gain of the rod cascade in terms of directly measured factors.

Laser Therapy Versus Anti-vegf Agents for Treatment of Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is characterized by abnormal retinal neurovascular development that occurs in preterm infants. Although in high-income countries up to 8% of childhood blindness is due to ROP, in middle-income countries this number rises to 40%. Moreover, as methods to ensure survival of preterm infants improve, the prevalence of ROP continues to increase. Worldwide, approximately 10% of births occur before the full gestational age defined as 37 weeks. The risk of developing ROP is inversely proportional to the infant’s gestational age and to its weight at the time of delivery, with most cases occurring in infants born at earlier than 28 weeks of gestation and weighing <1251 g. Although studies looking at ROP prevalence in various developed-world countries differ in the selection criteria for the infants at risk, incidence of any ROP ranges from 33% to 73%, whereas severe ROP was reported in 10% to 26% of patients. Understanding the pathology of ROP and its current treatments requires an understanding of the normal retinal vascular development. Retinal angiogenesis in humans begins at approximately 16th week of gestation, with vessels growing from the optic disc radially outwards. Normally, new vessels grow out from existing ones until they reach the ora serrata at around the time of full-term birth. In utero, the development of the sensory retina outpaces that of the retinal vasculature, and the resulting physiological hypoxia leads to the secretion of vasoactive factors such as vascular endothelial growth factor (VEGF), which, in turn, stimulate blood vessel growth. Premature birth, however, can disrupt normal retinal development and result in ROP. Two phases of ROP have been described. Phase I is characterized by the arrest of normal retinal vessel growth after a

Intermittent Horner syndrome in a pediatric patient.

Intermittent Horner syndrome is uncommon in both the adult and pediatric population. We describe a case of a pediatric patient with an intermittent Horner syndrome. Infrared photography and videography were used to help establish the diagnosis.

Phage Immunoprecipitation Sequencing of Autoantigens in Autoimmune Retinopathy

ABSTRACT Purpose: To identify autoantigens in autoimmune retinopathy patients by phage immunoprecipitation sequencing (PhIP-Seq), a new technique for autoantigen discovery. Methods: PhIP-Seq was used to sequence putative autoantibodies in plasma from 11 patients with autoimmune retinopathy and eight controls. We compared the autoantibodies’ molecular weights with those of proteins detected by Western blot. Results: Several autoantigens were found in cases and not detected in the controls. Autoantigens RTN3, PRPF6, TRPC6, and B3GNT8, four proteins expressed in the retina, were detected in plasma as autoantibodies from one patient each and no controls. Only one patient had an autoantibody, B3GNT8 (43.4 kDa), within a similar weight range as that detected by antiretinal antibody Western blot (42 kDa). Autoantibody POLR3A, which has a well-characterized role in scleroderma, was detected in two cases and no controls. Conclusion: PhIP-Seq detected autoantigens that are expressed in the retina as well as scleroderma-related autoantigens in autoimmune retinopathy patients.