CLT-004
CLT-004 is a small molecule anti-inflammatory compound that has demonstrated efficacy in reducing retinal inflammation and vascular permeability. CLT-004 has been formulated into nanoparticles, and current studies are underway to develop long-term efficacy profiles.
CLT-004 reduces retinal ICAM-1 levels in an STZ-diabetes model
ICAM-1 is a key initiator of the inflammatory cascade that causes immune cell infiltration into a tissue. Increases in ICAM-1 have been observed in the diabetic retina lead to leukostasis and vascular leakage. To examine the potency of CLT-004 in reducing ICAM-1, adult rats were injected with STZ to induce diabetes. Blood glucose levels were monitored to ensure the rats entered a diabetic state. At 3-weeks post-STZ injection, rats received an intravitreal injection of 30 mM CLT-004 in one eye, and the vehicle alone in the contralateral eye. After 1 day, the retinas were dissected, placed in extraction buffer, and sonicated. Following an overnight incubation, the samples were centrifuged and the supernatant was collected to examine the levels of soluble ICAM-1. ELISA analysis demonstrated a statistically significant decrease in ICAM-1 in retinas treated with CLT-004 as compared to controls, demonstrating the anti-inflammatory effect of CLT-004.
CLT-004 reduces vascular permeability in a STZ-diabetes model
As vascular permeability is a key component of visual loss associated with diabetes, we sought to examine whether CLT-004 demonstrated efficacy in reducing vascular leakage. Adult rats were made diabetic with STZ-injection, and blood glucose levels were monitored to ensure the rats entered a diabetic state. Following induction of diabetes with STZ, rats received an intravitreal injection of 5 µl of 30 mM CLT-004 in one eye and PBS/Cremophor in the contralateral eye. The rats then received an intravenous injection of Evans Blue which was allowed to circulate and permeate into any tissues with nearby vascular leakage. Following retinal extraction, the level of Evans blue dye was quantified and normalized to the total protein isolated from each samples. A decrease of over 70% in the level of Evans blue was observed in eyes receiving administration of 30 mM CLT-004 (mean ± SEM, n=5, p <0.05).