Ocular manifestations of central insulin resistance.

Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer's disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures.

αA-Crystallin Mediated Neuroprotection in the Retinal Neurons Is Independent of Protein Kinase B.

Phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway mediates pro-survival function in neurons. In the retina, PI3K/AKT/mTOR signaling pathway is related to the early pathogenesis of diabetic retinopathy. Signaling molecules in the membrane-initiated signaling pathway exhibiting neuroprotective function interacts with the PI3K/Akt pathway as an important survival pathway.

Evidence for Paracrine Protective Role of Exogenous αA-Crystallin in Retinal Ganglion Cells.

Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving small heat shock proteins such as α-crystallins. While initially considered as a purely intracellular mechanism, both αA-crystallins and αB-crystallins have been recently reported to be secreted by glial cells.

HspB4/αA-Crystallin Modulates Neuroinflammation in the Retina via the Stress-Specific Inflammatory Pathways.

Purpose: We have previously demonstrated that HspB4/αA-crystallin, a molecular chaperone, plays an important intrinsic neuroprotective role during diabetes, by its phosphorylation on residue 148. We also reported that HspB4/αA-crystallin is highly expressed by glial cells. There is a growing interest in the potential causative role of low-grade inflammation in diabetic retinopathy pathophysiology and retinal Müller glial cells' (MGCs') participation in the inflammatory response.

Evaluation of the possibility of selective modulation of retinal glucose transporters in diabetic complications: An experimental study.

Purpose: To identify the possibility of modulating retinal glucose transporters in diabetic conditions to prevent retinal complications of diabetic retinopathy.

Materials And Methods: In silico and in vitro binding assays were performed to assess the effect of genistein and positive controls (pioglitazone and estradiol) on nuclear receptor estrogen receptor beta and peroxisome proliferator-activated receptor gamma (PPARγ). In vivo effects of compounds were tested on diabetic rats.

Peripheral blood-derived monocytes show neuronal properties and integration in immune-deficient rd1 mouse model upon phenotypic differentiation and induction with retinal growth factors.

Background: Cell therapy is one of the most promising therapeutic interventions for retinitis pigmentosa. In the current study, we aimed to assess if peripheral blood-derived monocytes which are highly abundant and accessible could be utilized as a potential candidate for phenotypic differentiation into neuron-like cells.

Methods: The peripheral blood-derived monocytes were reconditioned phenotypically using extrinsic growth factors to induce pluripotency and proliferation.

Ocular kinetics and safety of intravitreally injected angiotensin converting enzyme inhibitor lisinopril.

Background And Objectives: The study investigated the intravitreal safety and vitreous disposition of lisinopril, an angiotensin converting enzyme inhibitor in rabbits for its projected use in retinopathy.

Methods: For the safety study, following the baseline ERG recording and fundus photography, 40 µg/50 µl of lisinopril sterile injection was injected unilaterally in the rabbit eyes (n = 4), where other eye served as a control. The electroretinogram and fundus images were obtained at 24, 48, 72 and 168 h following the intravitreal injection.

An experimental study to evaluate safety/toxicity of intravitreal natalizumab.

Purpose: The purpose of this prospective experimental study was to evaluate the safety/toxicity of α4β1 integrin blockade in rabbit retina using its monoclonal antibody (Natalizumab).

Methods: Twelve New Zealand albino rabbits were divided into three groups (n = 4). Unilateral intravitreal injections of three different concentrations of natalizumab were performed in every rabbit of each group (Group A: 0.

Un-segregated waste disposal: an alarming threat of antimicrobials in surface and ground water sources in Delhi.

Exposure of active pharmaceutical compounds (APCs) to the environment during human use is of potential importance in the emergence of drug resistance, changing soil microbiota and their residual effect on living organisms. Thus, this study aimed to assess the extent of exposure of APCs in the hydrologic cycle in and around New Delhi. This study analyzed the presence of 28 drugs from different classes in the surface water (river Yamuna) and aquifers collected from 48 places in Delhi (within the radius of 40 km).

Circulating biomarkers in glaucoma, age-related macular degeneration, and diabetic retinopathy.

Biomarkers to predict the altering physiological conditions over the period leading toward the ocular disorders are of major importance in therapeutics. Isolation and validation of the biomarkers specific to ocular diseases are a challenging task. Glaucoma is a neurodegenerative disease of the eye where the correlation of biomarkers in circulating fluid may be made specific for the eye.

A novel immunodeficient NOD.SCID mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration.

Retinitis pigmentosa (RP) is a common retinal degeneration disease caused by mutation in any gene of the photo transduction cascade and results in photoreceptor dystrophy. Over decades, several animal models have been used to address the need for the elucidation of effective therapeutics and factors regulating retinal degeneration to prohibit or renew the damaged retina. However, controversies over the immune privilege of retina during cell transplantation and the role of immune modulation during RP still remain largely uninvestigated because of the lack of suitable animal models.

Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention.

Objective: Examining the Retinal Renin Angiotensin System (RRAS) in the ROP neonates and analyzing the possibility of modulating the RRAS to prevent the progression in Oxygen Induced Retinopathy (OIR) model.

Method: Vitreous of ROP patients (n = 44, median age 5.5 months) was quantified for RRAS components, VEGF, HIF-1α and compared with age matched control.

Pharmacological Interventions for Vascular Targeting in Retinopathy of Prematurity: An Experimental Study.

Purpose: This study was conducted to evaluate the pharmacological interventions to target vascular proliferation in the Retinopathy of Prematurity (ROP).

Methods: Protein Kinase C modulator (Bryostatin), tubulin polymerization inhibitor (Dolastatin 10), antiVEGF (Bevacizumab) and a non-specific VEGF inhibitor (Thalidomide) were screened in Retinopathy of Prematurity (ROP) model. The retinal vasculature was evaluated by calculating the tortuosity indices of vessels and electroretinography responses in terms of ‘b’ wave amplitude and was recorded from ROP rats on postnatal Day 17 and Day 25.

Evaluation of hepatic metabolism and pharmacokinetics of ibuprofen in rats under chronic hypobaric hypoxia for targeted therapy at high altitude.

With studies indicative of altered drug metabolism and pharmacokinetics (DMPK) under high altitude (HA)-induced hypobaric hypoxia, consideration of better therapeutic approaches has continuously been aimed in research for HA related illness management. DMPK of drugs like ibuprofen may get affected under hypoxia which establishes the requirement of different therapeutic dose regimen to ensure safe and effective therapy at HA. This study examined the effects of the chronic hypobaric hypoxia (CHH) on hepatic DMPK of ibuprofen in rats.

Finger printing of counterfeit bevacizumab and identifying it before clinical use.

Background: Bevacizumab is widely used for ophthalmic purposes. Recently, counterfeit bevacizumab has become a matter of concern. We analysed samples of suspected counterfeit formulations of bevacizumab and assessed the possibility of using simple tests in the clinic by ophthalmologists to prevent the use of counterfeit preparations in patients.