Analysis of Macular Drusen and Blood Test Results in 945 <i>Macaca fascicularis</i>

<div><p>Age-dependent formation of macular drusen caused by the focal accumulation of extracellular deposits beneath the retinal pigment epithelium precede the development of age-related macular degeneration (AMD), one of the leading causes of blindness worldwide. It is established that inflammation contributes to the pathogenesis of drusen and AMD. However, development of a preemptive therapeutic strategy targeting macular drusen and AMD has been impeded by the lack of relevant animal models because most laboratory animals lack macula, an anatomic feature present only in humans and a subset of monkeys. Reportedly, macular drusen and macular degeneration develop in monkeys in an age-dependent manner. In this study, we analyzed blood test results from 945 <i>Macaca fascicularis</i>, 317 with and 628 without drusen. First, a trend test for drusen frequency (the Cochran–Armitage test) was applied to the quartile data for each parameter. We selected variables with an increasing or decreasing trend with higher quartiles at P < 0.05, to which multivariate logistic regression analysis was applied. This revealed a positive association of age (odds ratio [OR]: 1.10 per year, 95% confidence interval [CI]: 1.07–1.12) and white blood cell count (OR: 1.01 per 1 × 10³/μl, 95% CI: 1.00–1.01) with drusen. When the monkeys were divided by age, the association between drusen and white blood cell count was only evident in younger monkeys (OR: 1.01 per 1 × 10³/μl, 95% CI: 1.00–1.02). In conclusion, age and white blood cell count may be associated with drusen development in <i>M</i>. <i>fascicularis</i>. Systemic inflammation may contribute to drusen formation in monkeys.</p></div

Multiple logistic regression analysis and associated factors for retinal drusen.

<p>Multiple logistic regression analysis and associated factors for retinal drusen.</p

Basic biologic and hematologic data for monkeys with and without drusen.

<p>Basic biologic and hematologic data for monkeys with and without drusen.</p

Fundus of a monkey eye with drusen.

<p>Fundus photograph of a 21-year-old male <i>Macaca fascicularis</i> with drusen (open triangle; upper panel). Note retinal hemorrhage is seen inferiorly (filled triangle). Histologic section of an eye with drusen from another 34-year-old monkey. Note an accumulation of extracellular material underneath the retinal pigment epithelium consistent with drusen formation (*).</p

Multiple logistic regression analysis and associated factors for retinal drusen in 232 male and 713 female monkeys.

<p>Multiple logistic regression analysis and associated factors for retinal drusen in 232 male and 713 female monkeys.</p

Quartile analyses and trend tests in 945 monkeys.

<p>Quartile analyses and trend tests in 945 monkeys.</p

Comparison of Hb levels and MCVs and levels of iron metabolism markers between the baseline and the time of reduction in Hb level.

<p>Comparison of Hb levels and MCVs and levels of iron metabolism markers between the baseline and the time of reduction in Hb level.</p

Hemoglobin Decrease with Iron Deficiency Induced by Daclatasvir plus Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b - Fig 1

<p>Change in (A) MCV, (B) serum iron level, and (C) ferritin level at the time of the decrease in Hb level Median values and interquartile ranges are indicated. A paired <i>t</i> test was performed for MCVs and serum iron levels, and the Wilcoxon signed-rank test was performed for the ferritin levels.</p

Recovery of decreased Hb level after DCV/ASV treatment Mean values and SDs of the Hb levels at each time point are indicated.

<p>pre: the baseline Hb level, bottom: the lowest Hb level during DCV/ASV treatment, post 24W: Hb levels at 24 weeks after the DCV/ASV treatment.</p