1
|
Routh BL, Tripathi R, Giuliano E, Lujin P, Sinha PR, Mohan RR. Anti-fibrotic effects of lisinopril (ACE inhibitor) and fasudil (ROCK inhibitor) in combination for canine corneal fibrosis in vitro. Vet Ophthalmol 2024. [PMID: 39592228 DOI: 10.1111/vop.13304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 11/02/2024] [Accepted: 11/17/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Corneal fibrosis is a leading cause of blindness in mammalian species and may result in compromised performance in sports and daily functions. This study evaluated the safety and anti-fibrotic effects of the FDA-approved drugs, angiotensin-converting enzyme inhibitor (ACE-I) lisinopril and rho-kinase inhibitor (ROCK-I) fasudil, alone and in combination, on the canine cornea using an established in vitro model. METHODS To test the safety and efficacy of lisinopril and fasudil, primary canine corneal fibroblasts (CCFs) generated from donor corneas of healthy dogs (n = 20) were used. A series of dose-dependent and time-dependent assays with lisinopril (1-50 μM) and fasudil (1-10 nM) were performed. qRT-PCR, immunofluorescence (IF) staining, cell viability assay, cell proliferation assay, LIVE/DEAD viability/cytotoxicity assay, TUNEL assay, and total cell count were performed. RESULTS A 25-μM lisinopril and 3-nM fasudil dose were safe, nontoxic, and optimal for therapeutic evaluations in vitro. Treatments of lisinopril or fasudil, alone or in-combination, to CCFs grown in the presence of TGF-β1 (5 ng/mL) showed inhibition of myofibroblast formation based on phase-contrast microscopy. The qRT-PCR and IF studies showed a significant decrease in expression of profibrotic markers, including α-smooth muscle actin (α-SMA; p < .0001), fibronectin (FN; p = .0002), tenascin C (TNC; p < .0001), Collagen I (Col-I; p < .0001), Collagen IIIA1 (Co-IIIA1; p < .0001), and Collagen IV (Co-lV; p < .0001). CONCLUSION An ophthalmic formulation consisting of lisinopril and fasudil may offer a safe and effective method to treat canine corneal fibrosis. Additional studies evaluating safety and efficacy of this formulation in vivo are warranted.
Collapse
Affiliation(s)
- Brayden L Routh
- Department of Veterinary Medicine and Surgery, One-Health One-Medicine Ophthalmology and Vision Research Center, University of Missouri, Columbia, Missouri, USA
| | - Ratnakar Tripathi
- Department of Veterinary Medicine and Surgery, One-Health One-Medicine Ophthalmology and Vision Research Center, University of Missouri, Columbia, Missouri, USA
- Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA
| | - Elizabeth Giuliano
- Department of Veterinary Medicine and Surgery, One-Health One-Medicine Ophthalmology and Vision Research Center, University of Missouri, Columbia, Missouri, USA
| | - Payton Lujin
- Department of Veterinary Medicine and Surgery, One-Health One-Medicine Ophthalmology and Vision Research Center, University of Missouri, Columbia, Missouri, USA
| | - Prashant R Sinha
- Department of Veterinary Medicine and Surgery, One-Health One-Medicine Ophthalmology and Vision Research Center, University of Missouri, Columbia, Missouri, USA
| | - Rajiv R Mohan
- Department of Veterinary Medicine and Surgery, One-Health One-Medicine Ophthalmology and Vision Research Center, University of Missouri, Columbia, Missouri, USA
- Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA
- Mason Eye Institute, University of Missouri, Columbia, Missouri, USA
| |
Collapse
|
2
|
Musa M, Enaholo E, Bale BI, Salati C, Spadea L, Zeppieri M. Retinoscopes: Past and present. World J Methodol 2024; 14:91497. [PMID: 39310243 PMCID: PMC11230066 DOI: 10.5662/wjm.v14.i3.91497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 05/14/2024] [Accepted: 05/29/2024] [Indexed: 06/25/2024] Open
Abstract
BACKGROUND Retinoscopy is arguably the most important method in the eye clinic for diagnosing and managing refractive errors. Advantages of retinoscopy include its non-invasive nature, ability to assess patients of all ages, and usefulness in patients with limited cooperation or communication skills. AIM To discuss the history of retinoscopes and examine current literature on the subject. METHODS A search was conducted on the PubMed and with the reference citation analysis (https://www.referencecitationanalysis.com) database using the term "Retinoscopy," with a range restricted to the last 10 years (2013-2023). The search string algorithm was: "Retinoscopy" (MeSH Terms) OR "Retinoscopy" (All Fields) OR "Retinoscopes" (All Fields) AND [(All Fields) AND 2013: 2023 (pdat)]. RESULTS This systematic review included a total of 286 records. Publications reviewed iterations of the retinoscope into autorefractors, infrared photo retinoscope, television retinoscopy, and the Wifi enabled digital retinoscope. CONCLUSION The retinoscope has evolved significantly since its discovery, with a significant improvement in its diagnostic capabilities. While it has advantages such as non-invasiveness and broad applicability, limitations exist, and the need for skilled interpretation remains. With ongoing research, including the integration of artificial intelligence, retinoscopy is expected to continue advancing and playing a vital role in eye care.
Collapse
Affiliation(s)
- Mutali Musa
- Department of Optometry, University of Benin, Benin 300283, Nigeria
- Department of Ophthalmology, Africa Eye Laser Centre, Benin 300105, Nigeria
| | - Ehimare Enaholo
- Department of Ophthalmology, Africa Eye Laser Centre, Benin 300105, Nigeria
- Department of Ophthalmology, Centre for Sight Africa, Nkpor 434101, Nigeria
| | | | - Carlo Salati
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
| | - Leopoldo Spadea
- Eye Clinic, Policlinico Umberto I, "Sapienza" University of Rome, Rome 00142, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
| |
Collapse
|
3
|
Francis JM, Mowat FM, Ludwig A, Hicks JM, Pumphrey SA. Quantifying refractive error in companion dogs with and without nuclear sclerosis: 229 eyes from 118 dogs. Vet Ophthalmol 2024; 27:70-78. [PMID: 37986551 PMCID: PMC10842750 DOI: 10.1111/vop.13163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 11/03/2023] [Accepted: 11/09/2023] [Indexed: 11/22/2023]
Abstract
OBJECTIVE To evaluate the relationship between nuclear sclerosis (NS) and refractive error in companion dogs. ANIMALS STUDIED One hundred and eighteen companion dogs. PROCEDURES Dogs were examined and found to be free of significant ocular abnormalities aside from NS. NS was graded from 0 (absent) to 3 (severe) using a scale developed by the investigators. Manual refraction was performed. The effect of NS grade on refractive error was measured using a linear mixed effects analysis adjusted for age. The proportion of eyes with >1.5 D myopia in each NS grade was evaluated using a chi-square test. Visual impairment score (VIS) was obtained for a subset of dogs and compared against age, refractive error, and NS grade. RESULTS Age was strongly correlated with NS grade (p < .0001). Age-adjusted analysis of NS grade relative to refraction showed a mild but not statistically significant increase in myopia with increasing NS grade, with eyes with grade 3 NS averaging 0.58-0.88 D greater myopia than eyes without NS. However, the myopia of >1.5 D was documented in 4/58 (6.9%) eyes with grade 0 NS, 12/91 (13.2%) eyes with grade 1 NS, 13/57 (22.8%) eyes with grade 2 NS, and 7/23 (30.4%) eyes with grade 3 NS. Risk of myopia >1.5 D was significantly associated with increasing NS grade (p = .02). VIS was associated weakly with refractive error, moderately with age, and significantly with NS grade. CONCLUSIONS NS is associated with visual deficits in some dogs but is only weakly associated with myopia. More work is needed to characterize vision in aging dogs.
Collapse
Affiliation(s)
- Jenelle M Francis
- Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA
| | - Freya M Mowat
- Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Allison Ludwig
- Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Jacqueline M Hicks
- Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, USA
- Dr. Francis's current address is Animal Eye Clinic, Matthews, North Carolina, USA
| | - Stephanie A Pumphrey
- Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA
| |
Collapse
|
4
|
Balicka A, Zwolska J, Szadkowski M, Trbolova A, Balicki I. Refractive errors in mixed breed dogs of different ages. VET MED-CZECH 2023; 68:11-16. [PMID: 38384993 PMCID: PMC10878259 DOI: 10.17221/106/2021-vetmed] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 11/08/2022] [Indexed: 02/23/2024] Open
Abstract
The purpose of the study was to evaluate the occurrence and range of refractive errors in dogs of different ages. A total of 99 clinically healthy, mixed-breed mesocephalic dogs were included in the study and divided into three different age groups according to the current human/pet analogy chart: 40 adults (23 males, 17 females, 1-8 years old, 3-70 kg), 21 seniors (14 males, 7 females, 6-11 years old, 7-42 kg), and 38 geriatrics (22 males, 16 females, 8-13 years old, 5-45 kg). All the dogs underwent an ophthalmic examination, including Schirmer tear test, tonometry, biomicroscopy, and ophthalmoscopy. Neither eye drops nor pharmacological sedatives were administered before the autorefractometry. The refractive states were assessed bilaterally using a hand-held Retinomax 3 (Righton) autorefractor. The results underwent statistical analysis using Statistica v12 software (ANOVA and t-test). A P-value < 0.05 was considered as significant. Emmetropia, defined as a refractive state > -0.5 D and < +0.5 D, was found in 36% of the adult, 43% of the senior, and 38% of the geriatric patients. Anisometropia was found in 1% of the adult, 9.5% of the senior and 5.5% of the geriatric dogs when the refractive power of the two eyes differed ≥ 1.0 myopia ≤ -0.5 D and hyperopia ≥ +0.5 D were found in 23% and 41% of the adult eye globes as well as 24% and 33% in the senior dogs and 15% and 47% in the geriatric dogs, respectively. The maximal values of the myopia in the adult and geriatric dogs were -2.5 D and -2.75 D, respectively. The maximal values of the hyperopia in the adult and geriatric dogs were 1.75 D and 2.5 D, respectively. No statistically significant correlation was found between the groups. Ametropia is a common refractive state for dogs of different ages. The most frequent refractive state in ametropic mixed-bed dogs in all age groups is hyperopia.
Collapse
Affiliation(s)
- Agnieszka Balicka
- Small Animals Clinic, University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovak Republic
| | - Jowita Zwolska
- Department and Clinic of Animal Surgery, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Lublin, Poland
| | - Mateusz Szadkowski
- Department and Clinic of Animal Surgery, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Lublin, Poland
| | - Alexandra Trbolova
- Small Animals Clinic, University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovak Republic
| | - Ireneusz Balicki
- Department and Clinic of Animal Surgery, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Lublin, Poland
| |
Collapse
|