R. J. Collier

AL-78898A Inhibits Complement Deposition in a Primate Light Damage Model

PURPOSEnTo determine the association between ocular dominance and spherical/astigmatic anisometropia, age, and sex in hyperopic subjects.nnnMETHODSnThe medical records of 1274 hyperopic refractive surgery candidates were filtered. Ocular dominance was assessed with the hole-in-the-card test. Refractive error (manifest and cycloplegic) was measured in each subject and correlated to ocular dominance. Only subjects with corrected distance visual acuity of >20/22 in each eye were enrolled, to exclude amblyopia. Associations between ocular dominance and refractive state were analyzed by means of t-test, χ(2) test, Spearman correlation, and multivariate logistic regression analysis.nnnRESULTSnRight and left eye ocular dominance was noted in 57.4 and 40.5% of the individuals. Nondominant eyes were more hyperopic (2.6 ± 1.27 diopters [D] vs. 2.35 ± 1.16 D; P < 0.001) and more astigmatic (-1.3 ± 1.3 D vs. -1.2 ± 1.2 D; P = 0.003) compared to dominant eyes. For spherical equivalent (SE) anisometropia of >2.5 D (n = 21), the nondominant eye was more hyperopic in 95.2% (SE 4.7 ± 1.4 D) compared to 4.8% (1.8 ± 0.94 D; P < 0.001) for the dominant eye being more hyperopic. For astigmatic anisometropia of >2.5 D (n = 27), the nondominant eye was more astigmatic in 89% (mean astigmatism -3.8 ± 1.1 D) compared to 11.1% (-1.4 ± 1.4 D; P < 0.001) for the dominant eye being more astigmatic.nnnCONCLUSIONSnThe present study is the first to show that the nondominant eye has a greater degree of hyperopia and astigmatism than the dominant eye in hyperopic subjects. The prevalence of the nondominant eye being more hyperopic and more astigmatic increases with increasing anisometropia.

CEP Biomarkers as Potential Tools for Monitoring Therapeutics

Background Carboxyethylpyrrole (CEP) adducts are oxidative modifications derived from docosahexaenoate-containing lipids that are elevated in ocular tissues and plasma in age-related macular degeneration (AMD) and in rodents exposed to intense light. The goal of this study was to determine whether light-induced CEP adducts and autoantibodies are modulated by pretreatment with AL-8309A under conditions that prevent photo-oxidative damage of rat retina. AL-8309A is a serotonin 5-HT1A receptor agonist. Methods Albino rats were dark adapted prior to blue light exposure. Control rats were maintained in normal cyclic light. Rats were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0 hours) before light exposure for 6 h (3.1 mW/cm2, λ=450 nm). Animals were sacrificed immediately following light exposure and eyes, retinas and plasma were collected. CEP adducts and autoantibodies were quantified by Western analysis or ELISA. Results ANOVA supported significant differences in mean amounts of CEP adducts and autoantibodies among the light + vehicle, light + drug and dark control groups from both retina and plasma. Light-induced CEP adducts in retina were reduced ~20% following pretreatment with AL-8309A (n = 62 rats, p = 0.006) and retinal CEP immunoreactivity was less intense by immunohistochemistry. Plasma levels of light-induced CEP adducts were reduced at least 30% (n = 15 rats, p = 0.004) by drug pretreatment. Following drug treatment, average CEP autoantibody titer in light exposed rats (n = 22) was unchanged from dark control levels, and ~20% (p = 0.046) lower than in vehicle-treated rats. Conclusions Light-induced CEP adducts in rat retina and plasma were significantly decreased by pretreatment with AL-8309A. These results are consistent with and extend previous studies showing AL-8309A reduces light-induced retinal lesions in rats and support CEP biomarkers as possible tools for monitoring the efficacy of select therapeutics.