Topical Application of a Novel Harderian-Derived Nonpolar Lipid Prolongs Tear Film Breakup Time in Normal Beagle Dogs

Journal of Ocular Pharmacology and Therapeutics · 2025-09-23

PURPOSE: This preliminary study sought to determine the pharmacodynamic effect and tolerability of a novel rabbit-derived nonpolar lipid (rNPL593) on tear film breakup time (TFBUT) in healthy beagle dogs as a potential therapy for patients with evaporative dry eye disease. METHODS: In phase 1, two healthy beagle dogs received a single dose of rNPL593 at concentrations ranging from 0.1 to 10 mg/mL, and TFBUT was measured at different intervals post-dose in both eyes. In phase 2, five dogs received vehicle, 1 or 3 mg/mL rNPL593 once in both eyes, and TFBUT was measured at 6- and 24-h post-dose. In phase 3, three dogs received multiple doses of 3 mg/mL rNPL593 over 4 days, and TFBUT was performed 6 and 80 h after the final dose. Semiquantitative preclinical ocular toxicology scoring was performed in all phases to determine tolerability. RESULTS: In phase 1, topical treatment with 3 mg/mL rNPL593 resulted in a dose-dependent increase in TFBUT, assessed as the preferred concentration. In phase 2, the concentration of 3 mg/mL was superior to 1 mg/mL by creating a more pronounced and sustained increase in TFBUT over 24 h. In phase 3, there was an increase in TFBUT measured at 6-h post-dose that returned to baseline levels at 80-h post-dose. The topical rNPL593 was well tolerated in all phases with all doses. CONCLUSIONS: Treatment with rNPL593 was well tolerated at all doses tested and resulted in an increased TFBUT that was most pronounced with the 3 mg/mL concentration at 6- and 24-h post-dose.

Corneal Transplant Failure Is Associated With a High Percentage of Epithelial Downgrowth: A 24-Year Retrospective Clinical and Histological Study From a Single Academic Institute

Cornea · 2025-09-25

PURPOSE: Epithelial downgrowth (EDG) is a relatively infrequent complication of intraocular surgery or eye trauma. The literature is limited on this condition, and it remains a diagnostic challenge, both histologically and clinically. We have conducted a 24-year single-institution clinical and pathological retrospective review of EDG cases. METHODS: Cases of histologically suspected EDG were identified through the electronic record system at Casey Eye Institute Pathology Laboratory. Keywords entered in the search included "epithelial ingrowth" or "epithelial downgrowth" spanning the dates January 1999 to March 2023. RESULTS: Fifty-eight patients with suspected EDG on pathology were included in the study. Most patients had a complex surgical history, defined as 2 or more intraocular surgeries (64%; n = 37). History of nonsurgical ocular trauma was noted in 19% of cases (n = 12). The highest documented clinical presentations included corneal graft failure (52%; n = 30) and bullous keratopathy (12.5%; n = 8). Of the graft failure cases, 53% were penetrating keratoplasties (n = 16). EDG was clinically suspected in 16% of cases (n = 9). Overall, there has been an uptrend of histologically suspected cases from 1999 to present at our institute, with the highest number of suspected cases in the years 2018 to 2023 compared with the 1999 to 2005, 2006 to 2011, and 2012 to 2017 time intervals. CONCLUSIONS: EDG is diagnostically complex, and many suggestive features on pathology are not definitive. The frequency of cases with clinical suspicion for EDG and/or histopathologic features raising consideration of EDG have increased over a 24-year period. This study underscores the need for further research to aid in definitive diagnosis of EDG.

Black American ophthalmologists

Journal of the National Medical Association · 2025-12-04

Coniochaeta hoffmannii and mutabilis Invasive Fungal Keratitis: A Case Series and Literature Review

Eye Banking and Corneal Transplantation · 2024-02-29 · 1 citations

Purpose: To describe 2 Coniochaeta species ( Coniochaeta hoffmannii and Coniochaeta mutabilis ) as rare causes of invasive fungal keratitis resulting in enucleations and to provide a review of ocular infections caused by the genus Coniochaeta and underscore changes to its classification over the past 3 decades, which may clarify previous reports with outdated nomenclature. Methods: This is a small case series from a single academic institution (Casey Eye Institute) with a summary of the literature. Results: The first case describes a 53-year-old man who had an indolent but persistent anterior chamber reaction after repair of a penetrating nail injury. Cultures from a second penetrating keratoplasty identified C. hoffmannii , which was determined through phenotypic characterization and DNA sequencing. Despite surgical management, cultures were persistently positive for C . hoffmannii. Two years post-injury, he developed a funnel retinal detachment with proliferative vitreoretinopathy and elected for enucleation. The second case describes a 54-year-old woman with poor contact lens hygiene with a presumed filamentous fungal keratitis that remained refractory to topical natamycin. Broad-range polymerase chain reaction of an anterior chamber aspirate identified C. mutabilis. Therapeutic keratoplasty was performed for worsening infection; however, because of intractable pain, she elected for enucleation. Pathology from the enucleation specimen demonstrated persistent, but sparse, fungal elements. Conclusions: This is the first case series characterizing ocular infections caused by Coniochaeta , a rare cause of invasive fungal keratitis resulting in devastating outcomes for our patients. Identification of Coniochaeta was initially difficult by traditional culturing techniques, and subsequent molecular diagnostic testing proved useful in detection. Our review of ocular Coniochaeta clarifies previous reports with outdated nomenclature.

4 Supplementary Figures from Small Interfering RNA–Mediated Polo-Like Kinase 1 Depletion Preferentially Reduces the Survival of p53-Defective, Oncogenic Transformed Cells and Inhibits Tumor Growth in Animals

2023-03-30

4 Supplementary Figures from Small Interfering RNA–Mediated Polo-Like Kinase 1 Depletion Preferentially Reduces the Survival of p53-Defective, Oncogenic Transformed Cells and Inhibits Tumor Growth in Animals

4 Supplementary Figures from Small Interfering RNA–Mediated Polo-Like Kinase 1 Depletion Preferentially Reduces the Survival of p53-Defective, Oncogenic Transformed Cells and Inhibits Tumor Growth in Animals

2023-03-30

4 Supplementary Figures from Small Interfering RNA–Mediated Polo-Like Kinase 1 Depletion Preferentially Reduces the Survival of p53-Defective, Oncogenic Transformed Cells and Inhibits Tumor Growth in Animals

Data from Small Interfering RNA–Mediated Polo-Like Kinase 1 Depletion Preferentially Reduces the Survival of p53-Defective, Oncogenic Transformed Cells and Inhibits Tumor Growth in Animals

2023-03-30

<div>Abstract<p>Polo-like kinase 1 (Plk1) is required for multiple stages of mitosis and is up-regulated in many human malignancies. We depleted Plk1 expression using small interfering RNA (siRNA) and showed defects in bipolar spindle formation and cytokinesis, growth inhibition, and apoptosis induction in human cancer cell lines. To our surprise, depletion of Plk1 in normal human cells did not result in obvious cell cycle defects, and did not induce significant inhibition of cell growth for at least two cell cycles. In addition, Plk1 siRNA inhibited colony formation in soft agar and tumorigenesis in a HT1080 xenograft model in a dose-dependent manner. Analysis with isogenic pairs of cell lines, differing in p53 status, revealed that Plk1 depletion preferentially induced mitotic arrest, aneuploidy, and reduced cell survival in the p53-defective cell lines. No obvious defects were observed in most p53 wild-type cells during the first few cell cycles. In addition, long-term survival studies revealed that p53 facilitates survival upon Plk1 depletion. Therefore, short-term inhibition of Plk1 can kill tumor cells while allowing normal cells to survive. These data validate the episodic inhibition of Plk1 as a very useful approach for cancer treatment.</p></div>

Data from Small Interfering RNA–Mediated Polo-Like Kinase 1 Depletion Preferentially Reduces the Survival of p53-Defective, Oncogenic Transformed Cells and Inhibits Tumor Growth in Animals

2023-03-30

<div>Abstract<p>Polo-like kinase 1 (Plk1) is required for multiple stages of mitosis and is up-regulated in many human malignancies. We depleted Plk1 expression using small interfering RNA (siRNA) and showed defects in bipolar spindle formation and cytokinesis, growth inhibition, and apoptosis induction in human cancer cell lines. To our surprise, depletion of Plk1 in normal human cells did not result in obvious cell cycle defects, and did not induce significant inhibition of cell growth for at least two cell cycles. In addition, Plk1 siRNA inhibited colony formation in soft agar and tumorigenesis in a HT1080 xenograft model in a dose-dependent manner. Analysis with isogenic pairs of cell lines, differing in p53 status, revealed that Plk1 depletion preferentially induced mitotic arrest, aneuploidy, and reduced cell survival in the p53-defective cell lines. No obvious defects were observed in most p53 wild-type cells during the first few cell cycles. In addition, long-term survival studies revealed that p53 facilitates survival upon Plk1 depletion. Therefore, short-term inhibition of Plk1 can kill tumor cells while allowing normal cells to survive. These data validate the episodic inhibition of Plk1 as a very useful approach for cancer treatment.</p></div>

General Principles of Ophthalmic Pathology

2022-01-01 · 2 citations

Albert and Jakobiec's Principles and Practice of Ophthalmology

Springer eBooks · 2022 · 114 citations

• Ophthalmology
• Optometry
• Medicine