Complement Expression in the Retina is not Influenced by Short-term Pressure Elevation

Purpose: To determine whether short-term pressure elevation affects complement gene expression in the retina in vitro and in vivo. Methods: Muller cell (TR-MUL5) cultures and organotypic retinal cultures from adult mice and monkeys were sub- jected to either 24-h or 72-h of pressure at 0, 15, 30, and 45 mmHg above ambient. C57BL/6 mice were subjected to microbead-induced intraocular pressure (IOP) elevation for 7 days. RNA and protein were extracted and used for analysis of expression levels of complement component genes and complement component 1, q subcomponent (C1q) and comple- ment factor H (CFH) immunoblotting. Results: mRNA levels of complement genes and C1q protein levels in Muller cell cultures remained the same for all pressure levels after exposure for either 24 or 72 h. In primate and murine organotypic cultures, pressure elevation did not produce changes in complement gene expression or C1q and CFH protein levels at either the 24-h or 72-h time points. Pressure-related glial fibrillary acidic protein (GFAP) mRNA expression changes were detected in primate retinal organotypic cultures (analysis of variance [ANOVA]; p0.05 for both) with contralateral control and naïve control eyes. Conclusions: Short-term elevation of pressure in vitro as well as short-term (1 week) IOP elevation in vivo does not seem to dramatically alter complement system gene expression in the retina. Prolonged expression to elevated pressure may be necessary to affect the complement system expression

Visual Loss Induced by Adalimumab Used for Plaque Psoriasis

A 61-year-old Caucasian male with severe plaque psoriasis without joint involvement was initiated on adalimumab therapy. Shortly thereafter he presented to the emergency room with acute loss of vision in the right eye. A comprehensive systemic workup was instituted which included magnetic resonance imaging (MRI) with and without gadolinium of the brain and orbits. MRI revealed findings that were consistent with CNS demyelination and retrobulbar optic neuritis. Immediate cessation of adalimumab was instituted without any other systemic therapy. Complete return of vision occurred within 6 weeks. No additional psoriatic or neurologic treatment was instituted, and the patient has remained stable now for 14 months

IOPs of a subset (see Table 1) of male (A) and female (B) mice used in this study.

<p>Average IOP of male mice was not significantly different between the 3 genotypes (<i>p>0</i>.<i>09</i>, ANCOVA). In contrast, female C1qa -/- and C1qa +/- mice had higher IOPs than their C1qa +/+ littermates (<i>p<0</i>.<i>000001</i>, ANCOVA). Error bars represent standard errors of mean at each age.</p

Proportion of eyes from male (A, C, E) and female (B, D, F) congenic C1qa DBA/2 mice with various levels of RGC loss at 5–6 (A, B), 9–10 (C, D) and 11–13 (E, F) months of age.

<p>RGC loss was categorized as mild or no damage for eyes with RGC scores >8, moderate for eyes with scores >4 and ≤8 and severe for eyes with scores ≤4.</p

Mean (± SEM) number of intersections at various radii from the cell soma of retinal microglia located in the nerve fiber layer of eyes from male (A) and female (B) C1qa +/+ and C1qa -/- mice 6 months of age.

<p>Microglia images were obtained at a distance of 1000um from the optic nerve (2 per retina).</p

Numbers of eyes used for IOP determination at each age group.

<p>Numbers of eyes used for IOP determination at each age group.</p

Mean (± SEM) semi-quantitative ON scores of male (A) and female (B) congenic C1qa DBA/2 mice.

<p>Animals are grouped in three age groups: 5–6 months of age, 9–10 months of age and 11–13 months of age. Sample sizes: 22 C1q +/+, 32 C1q +/-, 12 C1q -/- at 5–6 months, 11 C1q +/+, 6 C1q +/-, 16 C1q -/- at 9–10 months and 11 C1q +/+, 36 C1q +/-, 18 C1q -/- at 11–13 months in male mice. 12 C1q +/+, 13 C1q +/-, 19 C1q -/- at 5–6 months, 11 C1q +/+, 17 C1q +/-, 13 C1q -/- at 9–10 months, 27 C1q +/+, 16 C1q +/-, 25 C1q -/- at 11–13 months in female mice. Statistically significant differences in post-hoc comparisons are indicated by a (*). NS: no statistical significance.</p

Correlation between semi-quantitative scoring and counting of RGCs (A) and ON axons (B).

<p>Linear regression coefficients (<i>R</i>^<i>2</i>) are indicated on the graphs.</p

Mean (± SEM) semi-quantitative RGC scores of male (A) and female (B) congenic C1qa DBA/2 mice and RGC counts of a subset of the eyes of male (C) and female (D) animals.

<p>Animals are grouped in three age groups: 5–6 months of age, 9–10 months of age and 11–13 months of age. Sample sizes: 18 C1q +/+, 19 C1q +/-, 22 C1q -/- at 5–6 months, 14 C1q +/+, 18 C1q +/-, 18 C1q -/- at 9–10 months and 13 C1q +/+, 34 C1q +/-, 22 C1q -/- at 11–13 months in male mice. 14 C1q +/+, 16 C1q +/-, 21 C1q -/- at 5–6 months, 11 C1q +/+, 21 C1q +/-, 16 C1q -/- at 9–10 months, 11 C1q +/+, 21 C1q +/-, 16 C1q -/- at 11–13 months in female mice. Only eyes from mice in the 9–10 and 11–13 age groups were subjected to RGC counting. Sample sizes: 9 C1q +/+, 14 C1q-/- at 9–10 months, 6 C1q +/+, 11 C1q -/- at 11–13 months in males, 7 C1q +/+, 10 C1q -/- at 9–10 months, 5 C1q +/+, 14 C1q -/- at 11–13 months in females. Statistically significant differences in post-hoc comparisons are indicated by a (*). NS: no statistical significance.</p