Abstract
Purpose :
Herpes Simplex Keratitis (HSK) is a purulent inflammation of the cornea caused by Herpes Simplex Virus (HSV). Acyclovir being the most common anti-viral is used against HSV-1 Keratitis but it fails to prevent latency, resulting in recurrence. Understanding the viral spread mechanism will help in development of effective therapies. The viral glycoproteins interact with Heparan Sulfate Proteoglycans (HSPG), a host cell receptor. Heparanase-1, an endo-β-glucuronidase degrades HSPG causing viral egression. In-vitro, HPSE expression is well explored but its implication in clinical specimens is still a challenge. So, the purpose of our study was to evaluate HPSE activity in the tear collected from individuals with HSV-1 keratitis and compare it with the non-viral forms.
Methods :
In this prospective and comparative study, tear samples (approximately 25-30 µl) were collected using capillary tubes from patients clinically diagnosed with HSV-1 (from both eyes, n=20), Bacterial and Fungal Keratitis (only infected eye, n=20). Healthy controls (n=20) were also included in the study. The HPSE activity in correlation with the HSPG was assessed according to the manufacturer’s instructions (Heparan Degrading Enzyme Assay Kit, CatLog No.: MK412, Takara Bio Inc., Japan). Statistical analysis was done using MyCurve fit.
Results :
From the study, it was found that the heparanase levels were significantly higher in case of viral keratitis when compared to bacterial (0.51±0.95 units/ml, p-value <0.0001), fungal (0.34±0.05 units/ml, p-value <0.0001) and controls (0.33±0.02 units/ml, p-value <0.00001). Moreover, the expression of heparanase was found to be higher in case of HSV-1 infected eyes (1.83±0.22 units/ml) in comparison to their contralateral eyes (1.33±0.15 units/ml, p-value= 0.033). There was no significant difference among the different forms of HSV-1 keratitis (p-value= 0.27).
Conclusions :
From the results we can conclude that using heparanase inhibitors, HPSE might be a used as promising therapeutic target for HSV-1 Keratitis. Though the difference in expression of heparanase was not statistically significant between the patients who presented with recurrent HSV-1 keratitis in comparison to the ones who presented for the first time, but there was an elevation in the heparanase levels in recurrent cases, however, including a larger cohort might give us a better idea.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.