Dataset Information

Cord Blood Serum (CBS)-Based Eye Drops Modulate Light-Induced Neurodegeneration in Albino Rat Retinas.

ABSTRACT: Age-related macular degeneration (AMD) is one of the leading causes of visual loss in western countries, it has no cure, and its incidence will grow in the future, for the overall population aging. Albino rats with retinal degeneration induced by exposure to high-intensity light (light-damage, LD) have been extensively used as a model of AMD to test neuroprotective agents. Among them, trophic factors (NGF and BDNF) have been shown to play a significant role in photoreceptors' survival. Interestingly, cord blood serum (CBS) is an extract full of chemokines and trophic factors; we, therefore, hypothesized that CBS could be an excellent candidate for neuroprotection. Here, we investigate whether CBS-based eye drops might mitigate the effects of light-induced retinal degeneration in albino rats. CBS treatment significantly preserved flash-electroretinogram (f-ERG) response after LD and reduced the "hot-spot" extension. Besides, CBS-treated animals better preserved the morphology of the outer nuclear layer, together with a reduction in microglia migration and activation. Interestingly, the treatment did not modulate reactive gliosis and activation of the self-protective mechanism (FGF2). In conclusion, our results suggest that CBS-based eye drops might be successfully used to mitigate retinal neurodegenerative processes such as AMD.

SUBMITTER: Di Marco S

PROVIDER: S-EPMC7277721 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Cord Blood Serum (CBS)-Based Eye Drops Modulate Light-Induced Neurodegeneration in Albino Rat Retinas.

Di Marco Stefano S Riccitelli Serena S Di Paolo Mattia M Campos Emilio E Buzzi Marina M Bisti Silvia S Versura Piera P

Biomolecules 20200428 5

Age-related macular degeneration (AMD) is one of the leading causes of visual loss in western countries, it has no cure, and its incidence will grow in the future, for the overall population aging. Albino rats with retinal degeneration induced by exposure to high-intensity light (light-damage, LD) have been extensively used as a model of AMD to test neuroprotective agents. Among them, trophic factors (NGF and BDNF) have been shown to play a significant role in photoreceptors' survival. Interesti ...[more]

PMID: 32354031

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Project description:BackgroundCurrent treatments for several corneal lesions show limited efficacy. Here we report the clinical evaluation of the efficacy of a novel eye drop preparation produced in a public cord blood (CB) bank.Material and methodsIn a multicentre, retrospective, consecutive case study we evaluated 33 patients (46 eyes) unresponsive to conventional treatments who required urgent intervention. The patients were given allogeneic eye drops obtained from cord blood platelet lysate (CBED) to treat severe ocular surface lesions under a compassionate use protocol. The CBED were prepared from CB units donated for haematopoietic stem cell transplantation that did not contain the minimum stem cell dose required for this use. Patients were grouped by acute conditions (neurotrophic ulcers: group I; other corneal ulcers: group II; corneal burns: group III), and chronic conditions (ocular graft-versus-host disease: group IV; severe dry eye syndrome: group V). The patients received one or two drops of the product to the affected eye four to six times per day for 19 days. A further 19-day cycle of treatment could be repeated according to the initial clinical response.ResultsPatients received a median of 19 CBED vials (interquartile range 19-57, range 19-442) to complete the therapy. Group I-II-III patients showed full and partial ulcer recovery in 25 (78%) and six (19%) eyes respectively. One eye (3%) did not respond to treatment. For groups IV-V improvement was reported for 12 (85%) eyes and lesions worsened on treatment in both eyes (15%) of one patient. No severe adverse events were directly attributed to CBED.DiscussionPromptly available CBED resulted in a well-tolerated allogeneic treatment that showed evidence of efficacy in this cohort of patients. These positive results support further studies on CBED from platelet lysate as a novel product of CB banks. A prospective clinical trial in neurotrophic keratitis (NCT03084861) is ongoing to confirm these preliminary data.

Project description:PurposeThe purpose of this study was to evaluate the intraocular pressure (IOP) reduction efficiency of hyaluronic acid-chitosan-latanoprost link nanoparticle (HA-CS-latanoprost link NP) formulated eye drops.MethodsThe IOP reduction study was performed in 24 normotensive albino rabbits. The test animals were randomized and grouped accordingly to treatment namely, HA-CS-latanoprost link NP, plain latanoprost, and the commercially available Xalatan eye drop, all were formulated with 0.005% latanoprost. The 9 days of the experiment were divided into baseline period (days 1-2), treatment period (days 3-6), and recovery period (days 7-9). A wireless noncontact tonometer was used to measure IOP at a time interval of 2 hours for 12 hours per day with 5 readings each.ResultsThe highest mean daily IOP reduction during the treatment period was 24% for plain latanoprost, 23% for Xalatan, and 29% for HA-CS-latanoprost link NP. The maximum reduction in IOP for plain latanoprost and Xalatan all occurred at the sixth hour with the peak effects of 4.85 mm Hg (37%) and 4.8 mm Hg (36%), respectively. Although HA-CS-latanoprost link NP had peak effects of 5.75 mm Hg (43%) at the sixth hour and 5.22 mm Hg (39%) at the eighth hour. Daily mean IOP measurements of each treatment group showed that HA-CS-latanoprost link NP has a greater IOP reduction effect compared with the other two treatments (P < 0.001).ConclusionsThe results showed that the formulation of latanoprost with CS and HA is more effective in reducing the IOP than by drug alone.Translational relevanceThe results provide evidence from animal experiment that HA-CS-latanoprost link NP formulation could improve and sustain drug concentration in the anterior segment of the eye. The improved reduction in IOP with that HA-CS-latanoprost link NP formulation can serve as a basis that latanoprost eye drops can be formulated with decreased concentration of benzalkonium HCl, an irritant preservative and penetration enhancer.

Project description:BACKGROUND:Dry eye may be caused or exacerbated by deficient lipid secretion. Recently, lipid-containing artificial tears have been developed to alleviate this deficiency. Our study compared the efficacy, safety, and acceptability of lipid-containing eye drops with that of aqueous eye drops. METHODS:A non-inferiority, randomized, parallel-group, investigator-masked multicenter trial was conducted. Subjects with signs and symptoms of dry eye were randomized to use one of two lipid-containing artificial tears, or one of two aqueous artificial tears. Subjects instilled assigned drops in each eye at least twice daily for 30 days. The primary efficacy analysis tested non-inferiority of a preservative-free lipid tear formulation (LT UD) to a preservative-free aqueous tear formulation (AqT UD) for change in Ocular Surface Disease Index (OSDI) score from baseline at day 30. Secondary measures included OSDI at day 7, tear break-up time (TBUT), corneal and conjunctival staining, Schirmer's test, acceptability and usage questionnaires, and safety assessments. RESULTS:A total of 315 subjects were randomized and included in the analyses. Subjects reported instilling a median of three doses of study eye drops per day in all groups. At days 7 and 30, all groups showed statistically significant improvements from baseline in OSDI (P<0.001) and TBUT (P?0.005). LT UD was non-inferior to AqT UD for mean change from baseline in OSDI score at day 30. No consistent or clinically relevant differences for the other efficacy variables were observed. Acceptability was generally similar across the groups and there was a low incidence of adverse events. CONCLUSION:In this heterogeneous population of dry eye subjects, there were no clinically significant differences in safety, effectiveness, and acceptability between lipid-containing artificial tears and aqueous eye drops. The results suggest that lipid-containing artificial tears can be used to counteract lipid deficiency that is common in dry eye, without compromising overall acceptability.

Dataset Information

Cord Blood Serum (CBS)-Based Eye Drops Modulate Light-Induced Neurodegeneration in Albino Rat Retinas.

Publications

Cord Blood Serum (CBS)-Based Eye Drops Modulate Light-Induced Neurodegeneration in Albino Rat Retinas.

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