Abstract
Purpose :
Choroideremia (CHM) is an X-linked, recessive chorioretinal dystrophy characterized by progressive degeneration of photoreceptors, retinal pigment epithelium, and the choroid. The view of CHM as a strictly ocular disease was contradicted by Zhang et. al in 2015, in the paper "Choroideremia Is a Systemic Disease With Lymphocyte Crystals and Plasma Lipid and RBC Membrane Abnormalities". We sought to confirm the findings.
Methods :
Blood samples were obtained from the subjects and age-matched controls and processed for imaging. Peripheral blood mononuclear cells and red blood cells were observed under transmission (TEM) and scanning electron microscopy (SEM) respectively. Additionally, images documented by Zhang et. al were evaluated by a cytopathologist.
We also analyzed the typical fatty acid (FA) profiles and concentrations of plasma phospholipids of 10 patients and compared this to a commercial standard.
Results :
TEM and SEM revealed no crystals or abnormalities in blood cells of CHM males or controls. Crystals observed by Zhang et al. in Figure 3E and 3F of the paper were identified by a pathologist as normal eosinophils.
Among saturated FAs, palmitic and stearic acid were most abundant in the CHM cohort. This plasma phospholipid FA profile is similar to an earlier study done by Holman et al (1994) on patients with retinitis pigmentosa, with depressed omega 3s and elevated total saturated acids.
Conclusions :
In contrast to Zhang et al., we found no evidence of crystals within, or on the surface of blood cells from CHM subjects, nor observed any appreciable difference from control cells. Zhang et al.'s “striking intracytoplasmic crystalline structures”, are in fact the characteristic secretory crystalloid granules of normal eosinophils, whose cores appear electron-dense under TEM; the finding is therefore unrelated to a diagnosis of CHM and not indicative of any pathological process.
Our evaluation of plasma phospholipid FA profile is not in agreement with Zhang et. al.'s study, which presented abnormal changes in plasma of CHM patients without showing a full profile of FAs, and only showed unusual FAs found at extremely low concentrations. Although we detected some increases in saturated fatty acids during the disease progressed by aging, the plasma fatty acid contribution to this disease seems minor. Our study did not replicate the finding that CHM is a systemic condition.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.