Journal of Ocular Pharmacology and Therapeutics最新文献

Posterior segment ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, are leading causes of vision impairment and blindness worldwide. Effective management of these conditions remains a formidable challenge due to the unique anatomical and physiological barriers of the eye, including the blood-retinal barrier and rapid drug clearance mechanisms. To address these hurdles, nanostructured drug delivery systems are proposed to overcome ocular barriers, target the retina, and enhance permeation while ensuring controlled release. Traditional therapeutic approaches, such as intravitreal injections, pose significant drawbacks, including patient discomfort, poor compliance, and potential complications. Therefore, understanding the physiology and clearance mechanism of eye could aid in the design of novel formulations that could be noninvasive and deliver drugs to reach the target site is pivotal for effective treatment strategies. This review focuses on recent advances in formulation strategies for posterior segment ocular drug delivery, highlighting their potential to overcome these limitations. Furthermore, the potential of nanocarrier systems such as in-situ gel, niosomes, hydrogels, dendrimers, liposomes, nanoparticles, and nanoemulsions for drug delivery more effectively and selectively is explored, and supplemented with illustrative examples, figures, and tables. This review aims to provide insights into the current state of posterior segment drug delivery, emphasizing the need for interdisciplinary approaches to develop patient-centric, minimally invasive, and effective therapeutic solutions.

Introduction: Povidone-iodine (PI) is the standard antiseptic for intravitreal injections (IVIs), while chlorhexidine (CHX) is a potential alternative. The efficacy of PI versus CHX in preventing endophthalmitis remains debated, with studies showing mixed results. Objective: To compare the effectiveness of using PI compared with CHX in IVI procedures regarding endophthalmitis rates, culture-positive endophthalmitis rates, and changes in visual acuity. Methods: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched the PubMed, EMBASE, Cochrane, and Web of Science databases for studies using PI compared with CHX in the IVI procedure. Statistical analysis was done using R software. Results: Four studies encompassing 453,340 eyes were included. The pooled results showed no statistical differences in endophthalmitis rates [odds ratio (OR): 1.26; 95% confidence interval (CI): 0.53-3.00]. In those who received the CHX group, there was no decrease in the rates of culture-positive endophthalmitis (OR: 2.04; 95% CI: 0.76-5.47), and the pooled results revealed no statistical differences in the mean change in visual acuity between the CHX and PI groups at final follow-up [mean difference: -0.02; 95% CI: -0.40 to 0.36]. Significant heterogeneity was identified in the post-procedure endophthalmitis rate and culture-positive endophthalmitis rate. Conclusions: Despite finding a trend toward higher rates of endophthalmitis with CHX, there are no statistical differences in using PI compared with CHX. However, our results are limited due to high heterogeneity. PI remains the gold standard, and a widespread shift to CHX cannot be justified based on the findings of this analysis.

Purpose: Cyclosporin A (CsA) is a drug used to prevent immune rejection in corneal transplantation. Most grafts performed today are endothelial grafts which are complicated with poor penetration of CsA into the endothelium due to its hydrophobicity. To improve CsA penetration into the corneal a new ocular formulation of CsA 2% with Miglyol was developed and is commercially available. The purpose of this pharmacokinetic study was to determine the concentrations of CsA in all layers of the cornea, in particular in the endothelium after topical administration of CsA 2%-Miglyol in rabbits. Methods: Sixteen rabbits were divided in 4 groups according to the time from the last instillation of CsA 2%-Miglyol to corneal sampling. Rabbit eyes received one drop of CsA twice a day for 5 days. Corneal tissue and plasma samples were collected at 2, 6, 12, and 24 h. CsA concentrations were measured using liquid chromatography-tandem mass spectrometry method. Results: Maximum concentrations (Cmax) of CsA were obtained in corneal tissues within 2 h after the last instillation of CsA 2%-Miglyol, except in the endothelium (12 h). Cmax were 59.75 ± 12.09 ng/mg, 15.66 ± 4.31 ng/mg, 5.17 ± 0.88 ng/mg, and 2.65 ± 0.47 ng/mg for the epithelium, endothelium, anterior stroma and posterior stroma. CsA concentrations remained high over a 24-h in all corneal layers. Conclusions: The topical application of CsA 2%-Miglyol allowed a high concentration of CsA in the corneal endothelium. The good penetration of CsA into the endothelium suggests that this formulation can be effective to prevent endothelial graft rejection.

Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due to its pivotal role in preserving cell membrane integrity and combating cellular oxidative damage. While its importance for overall health, including neurodegeneration, is acknowledged, the specific correlation between vitamin E deficiency and distinct ocular neurodegenerative disorders need to be further explored. This review delves into the molecular mechanisms of vitamin E in ocular neurodegenerative disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts, and emphasising the therapeutic implications drawn from existing evidence. Relationship between vitamin E and ocular neurodegenerative disorders is widely researched on, with its primary protective mechanisms attributed to its antioxidant and anti-inflammatory properties. However, studies on the supplementation of vitamin E among human subjects present mixed results, suggesting its complexities and variability depending on factors such as the specific disorder, disease stage, genetic differences, and form of vitamin E utilized. In conclusion, while vitamin E holds promise in mitigating ocular neurodegeneration through its antioxidant and anti-inflammatory properties, its supplementation's efficacy remains nuanced and context dependent. More research works are essential to elucidate its precise role and therapeutic potential in combating various ocular neurodegenerative disorders.

Purpose: To evaluate the efficacy of human placental extract (HPE) eye drops compared to that of carboxymethylcellulose (CMC) and human peripheral blood serum (HPBS) eye drops in a mouse model of experimental dry eye (EDE) and corneal alkali burns. Methods: EDE and alkali burn models were induced in C57BL/6 mice using desiccating stress and NaOH, respectively. In both the EDE and alkali burn models, treatment groups received CMC, HPBS, or HPE eye drops. In EDE model, tear volume, tear break-up time (TBUT), and total corneal fluorescein staining score (CFSS) were measured. ROS were detected with 2',7'-dichlorodihydrofluorescein diacetate. Conjunctiva goblet cells were identified by periodic acid-Schiff staining, and corneal epithelial apoptosis was detected by TUNEL assay. In alkali burn model, the area and diameter of epithelial defects were assessed in each group. Results: In the EDE model, tear volume, CFSS, and epithelial apoptosis were significantly improved in all treatment groups. Compared to the CMC group, the HPE group showed a better improvement in the production of tear volume, TBUT, CFSS, ROS, and conjunctiva goblet cell density. There were no significant differences in parameters between the HPBS and HPE groups except for TBUT at 14 days. In the alkali burn model, the HPE group had a smaller area compared to the control and CMC groups and a shorter diameter compared to the control group. Conclusion: HPE eye drops were as effective as HPBS eye drops in improving the clinical signs and ocular surface oxidative damage of EDE and in promoting corneal epithelialization after alkali burn.

Purpose: Renin-angiotensin system (RAS) is expressed in neuronal tissue and plays a role in neurodegenerative diseases involving excitotoxicity as a pathophysiological mechanism. In retina, excessive excitatory neurotransmission via N-methyl-d-aspartate (NMDA) receptors underlies neuronal apoptosis in conditions like glaucoma. However, it is not known if NMDA-mediated excitotoxicity alters retinal RAS expression. Hence, this study investigated the effect of NMDA exposure on the expression of RAS in rat retinas. Methods: Two groups of Sprague-Dawley rats received either phosphate buffer saline or NMDA (160 nmol). On day 7 posttreatment, retinal expression of RAS components including renin, angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin II (Ang II), Ang 1-7, Ang 1-9, MAS receptor, angiotensin II type 1 receptor (AT1R), ACE2, and aldosterone was measured using enzyme-linked immunosorbent assay and polymerase chain reaction. Morphometric studies were done to assess morphological alterations. Results: Following the exposure to NMDA, an upregulation of ACE expression was noted at both the protein (2.03-folds; P < 0.001) and mRNA (1.86-folds; P < 0.01) levels in rat retinas. AT1R protein and mRNA expression were greater by 1.73 (P < 0.0001) and 2.28-folds (P < 0.0001), respectively. However, mRNA expression for ACE2, Ang 1-7, and Ang 1-9, showed a 1.51-(P < 0.05), 2.41-(P < 0.001), and 2.37-(P < 0.0001) fold decrease. Ganglion cell layer (GCL) thickness and linear cell density in GCL were significantly lower in the NMDA-treated group (P < 0.05). Conclusions: NMDA exposure increases expression of the classical RAS and suppresses that of alternate RAS in rat retinas. These alterations are associated with retinal morphological changes indicating significant loss of neuronal cells in the GCL of rat retinas.

Purpose: This study aimed to investigate the effect of 13-cis retinoic acid (13-cis RA) on human meibomian gland epithelial cells (HMGECs) and explore the potential of using this experimental model as an in vitro approach for studying meibomian gland dysfunction (MGD). Methods: First, HMGECs were cultured with 13-cis RA at different doses and times, and cell viability and proliferation rates were assessed to determine the appropriate stimulation concentration and time. Subsequently, during the proliferation stage, the expression of proliferation, inflammation, and oxidative stress genes and their products were evaluated. The meibum synthesis capacity was determined during the differentiation stage. Additionally, the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662 was used as a control to assess the impact of 13-cis RA on PPARγ. Results: 13-cis RA significantly inhibited cell viability and proliferation in a time-dose response manner. Under the stimulation of 2 and 5 μM for 48 h during the proliferation stage, a significant decrease was observed in the expression of cell proliferation markers Ki67, antioxidant SOD-2, and Nrf-2. However, the expression of the pro-inflammatory factors IL-1β, IL-8, MMP9, and oxidative stress markers NOX-4 and reactive oxygen species increased. During the differentiation stage, it suppressed meibum synthesis and the expression of meibocyte differentiation-related proteins adipose differentiation-associated protein 4 (ADFP4), elongation of very long chain fatty acid protein 4 (ELOVL4), sterol regulatory element-binding protein 2 (SREBP-2), and PPARγ. Conclusion: 13-cis RA inhibited cell viability, promoted inflammation and oxidative stress, and suppressed meibum synthesis through the PPARγ pathway. Our study shed light on the effect of 13-cis RA on HMGECs and provided a promising direction for studying MGD in vitro.