Synchronous myopia development induced by bilateral form deprivation in chicks.

Form deprivation (FD) is a widely employed experimental paradigm, typically used to induce unilateral myopia in animal models. This model is weakened by potential influence upon the FD eye from vision in the freely-viewing contralateral eye, which could be eliminated by imposing FD in both eyes; but while a few previous studies have explored the feasibility of inducing bilateral FD in chicks, substantial discrepancies in treatment outcomes were noted. Consequently, this study aimed to establish a bilateral FD myopia model in chicks, with validation by investigating the associated ocular growth patterns, feeding, and social behavior. Six-day-old chicks were treated with bilateral (n = 21) or unilateral (n = 10) FD for 12 days; the fellow untreated eyes in the unilateral FD group served as controls. Refractive error, corneal power, and ocular axial dimensions were measured at 4-day intervals after the onset of form deprivation, with a Hartinger refractometer, a custom-made videokeratography system, and a high-resolution A-scan ultrasonographer, respectively. Body weight was monitored to assess the chick's physical development. Our results showed that birds treated with bilateral FD grew as robustly as the unilaterally form-deprived chicks, with similar or slightly heavier body weights and mortalities. Unilateral FD induced significantly higher myopia in the treated eye, with stronger corneal power, deeper anterior and vitreous chambers, and longer axial length. Moreover, either bilaterally or unilaterally FD eyes developed similar refractive error (bilateral FD, left: -28.03 ± 9.06 D, right: -28.44 ± 9.45 D; unilateral FD: -29.48 ± 8.26 D) and ocular biometric changes; but choroidal thickness was thicker in bilaterally FD eyes, rather than thinner as in unilaterally FD eyes. In addition to the highly synchronized (symmetrical, parallel) development reported previously in bilateral FD, we found in this study that the correlations between bilaterally form-deprived eyes were highest for ocular biometric parameters directly contributing to myopia development, including corneal power (r = 0.74 to 0.93), anterior chamber depth (r = 0.60 to 0.85), vitreous chamber depth (r = 0.92 to 0.94), and axial length (r = 0.90 to 0.96). The remarkably synchronized growth pattern confirmed the feasibility of the bilateral FD paradigm for future research on myopia.

Effect of Vitamin D on Retinoblastoma Protein in Prediabetic Individuals.

About 50.8 million people were diagnosed with diabetes in 2011; the count has increased by 10 million in the last five years. Type-1 diabetes could occur at any age, but predominantly in children and young adults. The risk of developing type II diabetes mellitus in the offspring of parents with DM II is 40% if one parent has DM II and approaches 70% if both parents have DM II. The process of developing diabetes from normal glucose tolerance is continuous, with insulin resistance being the first stage. As prediabetes progresses slowly to DM II, it may take approximately 15-20 years for an individual to become diabetic. This progression can be prevented or delayed by taking some precautions and making some lifestyle amendments, e.g., reducing weight by 5-7% of total body weight if obese, etc. Retinoblastoma protein is one of the pocket proteins that act as crucial gatekeepers during the G1/S transition in the cell cycle. A loss or defect in single- cell cycle activators (especially CDK4 and CDK6) leads to cell failure. In diabetic or stress conditions, p53 becomes a transcription factor, resulting in the transactivation of CKIs, which leads to cell cycle arrest, cell senescence, or cell apoptosis. Vitamin D affects insulin sensitivity by increasing insulin receptors or the sensitivity of insulin receptors to insulin. It also affects peroxisome proliferator-activated receptors (PPAR) and extracellular calcium. These influence both insulin resistance and secretion mechanisms, undertaking the pathogenesis of type II diabetes. The study confines a marked decrement in the levels of random and fasting blood glucose levels upon regular vitamin D intake, along with a significant elevation of retinoblastoma protein levels in the circulatory system. The most critical risk factor for the occurrence of the condition came out to be family history, showing that patients with first-degree relatives with diabetes are more susceptible. Factors such as physical inactivity or comorbid conditions further aggravate the risk of developing the disease. The increase in pRB levels caused by vitamin D therapy in prediabetic patients directly influences blood glucose levels. pRB is supposed to play a role in maintaining blood sugar levels. The results of this study could be used for further studies to evaluate the role of vitamin D and pRB in regeneration therapy for beta cells in prediabetics.

Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia.

PURPOSE: We previously reported differential gene expression of the bone morphogenetic protein 2 (Bmp2) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia. METHODS: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular -10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2, Id3, and Nog genes. RESULTS: Mean interocular differences (treated-control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia (p < 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear (p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day (p = 0.012 and 0.016) and 7 days (p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day (p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation.

Experimentally induced myopia and myopic astigmatism alter retinal electrophysiology in chickens.

Myopia (or "short-sightedness") and astigmatism are major causes of visual impairment worldwide. Significant amounts of astigmatism are frequently observed in infants and have been associated with myopia development. Although it is well established that both myopia and astigmatism are associated with ocular structural changes from anterior to posterior segments, very little is known on how these refractive errors alter retinal functions. This study investigated the effects of experimentally induced myopia and myopic-astigmatism on retinal electrophysiology by using an image-guided, multifocal global flash stimulation in chickens, a widely used animal model for refractive error development. Myopia and myopic-astigmatism were experimentally induced, respectively, by wearing spherical (- 10 D, n = 12) and sphero-cylindrical lenses (- 6.00 DS/- 8.00 DCx90: Hyperopic With-The Rule, H-WTR, n = 15; - 6.00 DS/- 8.00 DCx180: Hyperopic Against-The-Rule, H-ATR, n = 11) monocularly for a week (post-hatching day 5 to 12). An aged-matched control group without any lens treatment provided normal data (n = 12). Multifocal electrophysiological results revealed significant regional variation in the amplitude of induced component (IC) (central greater than peripheral; both p < 0.05) in the normal and H-ATR groups, but not in the - 10 D and H-WTR groups. Most importantly, for the first time, our results showed that both H-WTR and H-ATR groups exhibited a significantly longer implicit time of the inner retinal response at the central region when compared to the normal and - 10 D groups, highlighting a significant role of astigmatism in retinal physiology.

Multicompartment systems: A putative carrier for combined drug delivery and targeting.

In this review, we discuss recent developments in multicompartment systems commonly referred to as vesosomes, as well as their method of preparation, surface modifications, and clinical potential. Vesosomal systems are able to entrap more than one drug moiety and can be customized for site-specific delivery. We focus in particular on the possible reticuloendothelial system (RES) - mediated accumulation of vesosomes, and their application in tumor targeting, as areas for further investigation.

Tenon's Patch Graft: A Review of Indications, Surgical Technique, Outcomes and Complications.

PURPOSE: Corneal perforations are common corneal emergencies faced by ophthalmologists across the globe. There are multiple modalities of management, most of which require an eye bank support or availability of tissue adhesives. Tenon's patch graft (TPG) is a technique that does not depend on these factors as the graft is harvested from the same eye of the patient. The aim of this review is to provide an overview of the indications, technique, normal postoperative course, and management of complications. METHODS: After carrying out a literature search on "tenon's capsule", "corneal patch graft", "tenon's patch graft", "multilayered amniotic membrane" and "corneal perforations", 28 articles were included for this review. RESULTS: TPG graft can be performed in cases of small to moderate perforations without active suppuration. The procedure can also be combined with amniotic membrane grafting or tissue adhesives to provide additional tectonic support. Postoperatively, the epithelium heals over a course 2-3 weeks and restoration of a stable ocular surface with a corneal scar is completed by the third postoperative month. Complications following the surgical procedure are rare but can include graft displacement, melt and pseudoectasia. Subsequent visual rehabilitation with contact lenses or keratoplasties can be planned in these eyes that yields good visual outcomes. CONCLUSIONS: Tenon's patch graft is a simple yet viable option in management of small to moderate corneal perforations. The procedure does not necessitate the prior availability of specialized products and can be performed with routine equipment of an ophthalmic theatre, making it an attractive option in low resource settings.

Early Astigmatism Can Alter Myopia Development in Chickens.

Purpose: To determine the effects of optically imposed astigmatism on myopia development in chickens. Methods: Chicks were randomly assigned to wear either spherical (-10D, "LIM", n = 14) or sphero-cylindrical lenses (n ≥ 19 in each group) monocularly for a week from 5 days of age. All lenses imposed the same magnitude of spherical-equivalent hyperopic defocus (-10D), with the two astigmatic magnitudes (-8D or -4D) and four axes (45°, 90°, 135°, or 180°) altered to simulate four subtypes of clinical astigmatism. At the end of the treatment, refractive state was measured for all birds, whereas ocular axial dimensions and corneal curvature were measured for subsets of birds. Results: Sphero-cylindrical lens wear produced significant impacts on nearly all refractive parameters (P < 0.001), resulting in myopic-astigmatic errors in the treated eyes. Compared to LIM, the presence of astigmatic blur induced lower myopic error (all except L180 group, P < 0.001) but with higher refractive astigmatism (all P < 0.001) in birds treated with sphero-cylindrical lenses. Distributions of the refractive, axial, and corneal shape parameters in the sphero-cylindrical lens-wear groups indicated that the astigmatic blur had directed the eye growth toward the least hyperopic image plane, with against-the-rule (ATR) and with-the-rule (WTR) astigmatisms typically inducing differential biometric changes. Conclusions: The presence of early astigmatism predictably altered myopia development in chicks. Furthermore, the differential effects of WTR and ATR astigmatisms on anterior and posterior segment changes suggest that the eye growth mechanism is sensitive to the optical properties of astigmatism.

Dual antitubercular drug loaded liposomes for macrophage targeting: development, characterisation, ex vivo and in vivo assessment.

AIM: The present study was conducted to formulate and investigate liposomes for the dual drug delivery based on anti-tubercular drug(s) combination i.e. Isoniazid (INH) and Rifampicin (RIF). MATERIALS AND METHODS: Mannosylated and non mannosylated liposomes were prepared by lipid thin film hydration method, using DSPC: Chol at a molar ratio 6:4 while in case of mannosylated liposomes DSPC: Chol: Man-C4-Chol at a molar ratio 6.0:3.5:0.5 were used and extensively characterised. The particle size and zeta potential were recorded to be 1.29 ± 0.24 µm and -9.1 ± 0.11 mV. The drug entrapment (%) was recorded to be 84.7 ± 1.25% for Rifampicin and 31.8 ± 0.12% for Isoniazid. RESULTS: The antitubercular activity studied in Balb/C mice was maximum in the case of mannosylated liposomes. The biodistribution studies also revealed higher drug(s) concentration (accumulation) maintained over a protracted period. CONCLUSIONS: The liposomal preparations are passively as well as actively uptaken by the alveolar macrophages which are the cellular tropics of infection. The mannosylated liposomes appear to be a potential carrier for dual drug delivery and targeted antitubercular therapy.

Development and Characterization of Biocompatible Mannose Functionalized Mesospheres: an Effective Chemotherapeutic Approach for Lung Cancer Targeting.

The aim of the present study was to analyze the lung targeting potential of surface engineered mesospheres loaded with doxorubicin hydrochloride (DOX). Gelatin-based DOX encapsulated mesospheres were prepared using a steric stabilization process and surface modified with mannose, using the amino group present on the surface of the mesospheres. Gelatin-DOX-mesospheres (M1) and gelatin-mannosylated-DOX-mesospheres (M2) were characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found respectively 8.7 ± 0.35, 0.671 ± 0.018, 1.74 ± 0.27, and 80.4 ± 1.2 for (M1) and 9.8 ± 0.41, 0.625 ± 0.010, 0.85 ± 0.11, and 75.1 ± 0.7 for (M2). Furthermore, the mesospheres were characterized by FTIR, DSC, SEM, and TEM. In vitro drug release study of optimized formulation was carried out using the dialysis tube method. The cumulative percent drug release was found to be 79.2 ± 0.1% and 69.6 ± 0.52% respectively for gelatin-DOX-mesospheres and gelatin-mannosylated-DOX-mesospheres. In vitro cytotoxicity of formulations was determined using xenograft A-549 tumor cell lines. The cytotoxicity recorded as IC50 was more in the case of M2 compared to M1. In addition, mesospheres exhibited minimal hemolytic toxicity and appear to be promising for sustained drug delivery of DOX to the lungs. Cytotoxicity assay was conducted on the A-549 cell line. The results revealed that gelatin-mannosylated-DOX-mesospheres were maximally cytotoxic as compared to free DOX as well as gelatin-DOX-mesospheres. The lung's accumulation of drug was measured and found maximum after administration of M2. It may, therefore, be inferred that gelatin-mannosylated-DOX-mesospheres are capable to carry bioactive(s) and can be used specifically to target the lung cancer with minimal side effects.

Lipid Drug Conjugates for Improved Therapeutic Benefits.

Lipid drug conjugates (LDCs) are the chemical entities, which are commonly referred to as lipoidal prodrug. They contain the bioactive molecules, covalently or non-covalently linked with lipids like fatty acids, glycerides or phospholipids. Lipid drug conjugates are fabricated with the aim of increasing drug payload. It also prevents leakage of a highly polar bioactive(s) from the lipophilic matrix. Conjugating lipidic moieties to bioactive molecules improves hydrophobicity. It also modifies other characteristics of bioactive(s). These conjugates possess numerous merits encompassing enhanced tumor targeting, lymphatic system targeting, systemic bioavailability and decreased toxicity. Different conjugation approaches, chemical linkers and spacers can be used to synthesize LDCs based on the chemical behaviour of lipidic moieties and bioactive(s). The factors such as coupling/ conjugation methods, the linkers etc. regulate and control the release of bioactive(s) from the LDCs. It is considered as a crucial parameter for the better execution of the LDCs. The purpose of this review is to explore widely the potential of LDCs as an approach for improving the therapeutic indices of bioactive(s). In this review, the conjugation methods, various lipids used for preparing LDCs, and advantages of using LDCs are summarized. Though LDCs might be administered without using a carrier; however, majority of them are incorporated in an appropriate nanocarrier system. In the conjugates, the lipidic component may considerably improve the loading of lipoidal bioactive(s) in the lipid compartments. This results in high % drug entrapment in nanocarriers with greater stability. Several nanometric carriers such as polymeric nanoparticles, micelles, liposomes, emulsions and lipid nanoparticles, which have been explored, are reviewed here.

Lipid-Based Nanocarriers for Lymphatic Transportation.

The effectiveness of any drug is dependent on to various factors like drug solubility, bioavailability, selection of appropriate delivery system, and proper route of administration. The oral route for the delivery of drugs is undoubtedly the most convenient, safest and has been widely used from past few decades for the effective delivery of drugs. However, despite of the numerous advantages that oral route offers, it often suffers certain limitations like low bioavailability due to poor water solubility as well as poor permeability of drugs, degradation of the drug in the physiological pH of the stomach, hepatic first-pass metabolism, etc. The researchers have been continuously working extensively to surmount and address appropriately the inherent drawbacks of the oral drug delivery. The constant and continuous efforts have led to the development of lipid-based nano drug delivery system to overcome the aforesaid associated challenges of the oral delivery through lymphatic transportation. The use of lymphatic route has demonstrated its critical and crucial role in overcoming the problem associated and related to low bioavailability of poorly water-soluble and poorly permeable drugs by bypassing intestinal absorption and possible first-pass metabolism. The current review summarizes the bonafide perks of using the lipid-based nanocarriers for the delivery of drugs using the lymphatic route. The lipid-based nanocarriers seem to be a promising delivery system which can be optimized and further explored as an alternative to the conventional dosage forms for the enhancement of oral bioavailability of drugs, with better patient compliance, minimum side effect, and improved the overall quality of life.

Nanocarrier-Based Combination Chemotherapy for Resistant Tumor: Development, Characterization, and Ex Vivo Cytotoxicity Assessment.

A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found to be 196 ± 2.5 nm, 0.214 ± 0.04, +23.4 ± 0.3 mV and 88.3 ± 0.2% (PTX), and 89.6 ± 0.5% (DOX) respectively. In vitro drug release study of optimized formulation was carried out using dialysis tube method. FA-conjugated PTX-DOX-loaded NLCs showed 75.6 and 78.4% (cumulative drug release) of PTX and DOX respectively in 72 h in PBS (pH 7.4)/methanol (7:3), while in the case of FA-conjugated PTX-DOX-loaded NLCs, cumulative drug release recorded was 80.4 and 82.8% of PTX and DOX respectively in 72 h in PBS (pH 4.0)/methanol (7:3). Further, the formulation(s) were evaluated for ex vivo cytotoxicity study. The cytotoxicity assay in doxorubicin-resistant human breast cancer MCF-7/ADR cell lines revealed lowest GI50 value of FA-D-P NLCs which was 1.04 ± 0.012 µg/ml, followed by D-P NLCs and D-P solution with GI50 values of 3.12 ± 0.023 and 3.89 ± 0.007 µg/ml, respectively. Findings indicated that the folic acid-conjugated PTX and DOX co-loaded NLCs exhibited lower GI50 values as compared to unconjugated PTX and DOX co-loaded NLCs; thus, they have relatively potential anticancer efficacy against resistant tumor.

Knowledge and practice patterns of Intensive Care Unit nurses towards eye care in Chhattisgarh state.

Purpose: The aim of the study was to present the level of knowledge and practice patterns regarding exposure keratopathy in mechanically ventilated patients among Intensive Care Unit (ICU) nurses in Chhattisgarh state. Methods: A previously validated semi-structured questionnaire was administered in the ICU of six multispecialty hospitals in Chhattisgarh in 2014-2015. Demography included age, gender, level of education, and months of working in ICU. Most of the questions dealt with frequency of eyelid closure assessment, frequency of cleaning of eyes with saline gauze, using a protocol-based approach for eye care, and documentation of ophthalmic complications. Common barriers to delivery of eye care such as shortage of time and too much writing tasks were also inquired. Results: Our study included 120 nurses. They worked for mean 22.9 ± 17.8 months in ICU. Knowledge about high risk of exposure keratopathy in ventilated patient was present in 93% (78%; 95% confidence interval [CI]) nurses. Only six nurses (5%) followed a strict protocol for eye care, 52 nurses (43%) checked for eyelid closure in the ventilated patients, and 58 (48%) cleaned the eyes frequently. Those who were aware of exposure keratopathy checked eyelid closure (73% vs. 48%) and cleaned eyes with saline gauze more frequently (24% vs. 4%). Nurses in cardiac ICU were significantly lesser aware of exposure complications compared to medical ICU nurses (40% reduction in awareness, 95% CI = 0.37-0.98, P = 0.04). Conclusion: Although there is high awareness, practice patterns of ICU nurses were less than desired. Educational initiatives should focus on weaknesses in knowledge and practice noted to improve eye care of patients in ICU.