Antibiotics delivered through conventional dosage against ophthalmic infections show lower therapeutic efficacy due to their low residence time. Therefore, there is a great need to design and develop novel dosage forms that would increase the ocular residence time of antibiotics at the site of infection. This study describes the development of nanoparticles laden in situ gelling solution, intended to sustain antibiotic release for improved therapeutic efficiency. Oxytetracycline-loaded gelatin-polyacrylic acid nanoparticles were prepared and incorporated in poloxamer-N407 solution. The rheological properties of the system were studied concerning time and temperature. Moreover, in vivo biocompatibility of the system was ascertained using the Draize test and histological studies. Finally, the optimized formulation was evaluated for in vitro antibacterial activity against one of the most common keratitis causing bacteria, Pseudomonas aeruginosa. Additionally, the in vivo efficacy was evaluated on the rabbit’s eye conjunctivitis model. The formulation showed a sustained effect against keratitis; furthermore, the antibacterial activity was comparable with the commercial product.

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Mesenchymal stem cells are currently studied as therapeutic strategy for management of DR. Exosomes, considered as a promising cell-free therapy option, display biological functions similar to those of their parent cells. In retinal development, Wnt/b-catenin signaling provides key cues for functional progression. The present study aimed to evaluate the potential efficacy of bone marrow-derived mesenchymal stem cell-derived exosomes (BM-MSCs-Ex) in diabetes-induced retinal injury via modulation of the Wnt/ b-catenin signaling pathway. Eighty-one rats were allocated into 6 groups (control, DR, DR + DKK1, DR + exosomes, DR + Wnt3a and DR + exosomes+Wnt3a). Evaluation of each group was via histopathological examination, assessment of gene and/or protein expression concerned with oxidative stress (SOD1, SOD2, Nox2, Nox4, iNOS), inflammation (TNF-α, ICAM-1, NF-κB) and angiogenesis (VEGF, VE-cadherin). Results demonstrated that exosomes blocked the wnt/b-catenin pathway in diabetic retina concomitant with significant reduction of features of DR as shown by downregulation of retinal oxidants, upregulation of antioxidant enzymes, suppression of retinal inflammatory and angiogenic markers. These results were further confirmed by histopathological results, fundus examination and optical coherence tomography. Additionally, exosomes ameliorative effects abrogated wnt3a-triggered retinal injury in DR. Collectively, these data demonstrated that exosomes ameliorated diabetes-induced retinal injury via suppressing Wnt/ b-catenin signaling with subsequent reduction of oxidative stress, inflammation and angiogenesis.

Background: The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized core liposomes (GCLs) were fabricated to increase the drug entrapment, corneal penetration, and physical stability of the investigated molecule. Research Design and Methods: GCLs encapsulating BRT were prepared and optimized utilizing D-optimal design (DOD). The effect of plasticizer incorporation on the physicochemical characteristics and on the in vivo performance was studied. The optimized formulations were investigated for pH, rheological properties, morphological characteristics, in vitro release profiles, biological performance, safety profile. The effects of storage and gamma sterilization were also investigated. Results: The results revealed the great success of the prepared formulations to achieve high entrapment efficiency reaching 98% after a maturation period of 10 days. The addition of glycerol as plasticizer significantly minimized the particle size and shortened the maturation period to 7 days. The selected formulations were stable for 3 months after gamma sterilization. The formulations showed significant lowering of intra-ocular pressure (IOP) in glaucomatous rabbits with sustainment of the pharmacological effect for 24 hours compared to drug solution. Conclusions: Enhanced in vitro and in vivo profiles of brimonidine tartrate loaded gelatinized-core-liposomes were obtained.

Alzheimer’s disease (AD) is one of the most serious neurodegenerative diseases in the globe. As a result, there is an acute need to discover indications that allow for early disease detection. There is growing scientific data showing the similarities between the eye and other central nervous system components, suggesting that information obtained in ophthalmic research might be valuable in the study and diagnosis of AD. Fifty male albino Wistar rats were separated into five groups: the first group served as control, and the other four groups of animals were administrated aluminium chloride (AlCl3) in a dose of 100 mg/kg body weight (b.w.) for 2, 4, 6, and 8 weeks, respectively. Insights into the function of the retina by electroretinogram (ERG) and the changes thought to have occurred in the molecular structure of the retina and brain using Fourier transform infrared spectroscopy (FTIR) as a result of AD progression induced by AlCl3 in rats were done. Moreover, the measurement of acetylcholinesterase (AchE) was done. After 6 and 8 weeks of AlCl3 injection, there was a substantial reduction ( $p\le 0.05$ ) in a- and b-wave amplitudes and a significant rise ( $p\le 0.05$ ) in implicit time compared to controls. A significant elevation ( $p\le 0.05$ ) of AchE content was observed after 4, 6, and 8 weeks. FTIR revealed a significant increase ( $p\le 0.05$ ) of β-turn and β-sheet content associated with significant decrease ( $p\le 0.05$ ) of α-helix content for all groups administrated with AlCl3. Our findings suggest that retinal biomarkers such as ERG of the retina may be used as a screening tool for detection of AD. Secondary structural changes in the proteins of the retina and the brain were similar in AD rats’ model and precede retinal dysfunction.

This approach aimed to assess the therapeutic significance of BM-MSCs in alleviating LSCD elicited in rats via corneal alkali burns and to explore the associated repairing mechanisms. Rats were assigned to (1) control group, (2) alkali burn group, and (3) stem cells group. Corneal surface investigations were performed using a slit lamp and fluorescence tests. The therapeutic impact of BM-MSCs was appraised by estimating the protein levels of TNF-α, SOD, VEGF, MMP-2, and IL-8 using ELISA. Moreover, mRNA transcription levels of corneal TNF-α, NF-kB, COX-2, and caspase-3 were quantified. Histological investigation and immunostaining of corneal cytokeratin 3 and p63 proteins were also conducted. The results indicated that BM-MSCs treatment enhanced the corneal wound healing, decreased corneal opacity, and neovascularization. Moreover, such treatment resulted in a significant decline in corneal TNF-α, IL-8, VEGF, and MMP-2 protein levels. Additionally, stem cells group elicited a significant down-expression of TNF-α, NF-κB, COX-2, and caspase-3 genes. Besides, BM-MSCs treatment restored the corneal epithelial integrity and ameliorated the pathological characteristics, as confirmed by histological and immunohistochemical analysis. Conclusively, the present investigation underscores the healing ability of BM-MSCs in LSCD in the rat model by repairing the damaged corneal epithelium through withstanding inflammation, angiogenesis, and apoptosis. Consequently, MSCs transplantation represents a promising therapeutic modality for LSCD.