The human retina provides vision at light levels ranging from starlight to sunlight. Its supporting tissues regulate plasma-delivered lipophilic essentials for vision, including retinoids. The macula is an anatomic specialization for high-acuity and color vision that is also vulnerable to prevalent blinding diseases. The retina’s exquisite architecture comprises numerous cell types that are aligned horizontally, yielding structurally distinct cell, synaptic, and vascular layers that are visible in histology and in diagnostic clinical imaging. MALDI imaging mass spectrometry (IMS) is now capable of uniting low micrometer spatial resolution with high levels of chemical specificity. In this study, a multimodal imaging approach fortified with accurate multi-image registration was used to localize lipids in human retina tissue at laminar, cellular, and subcellular levels. Multimodal imaging results indicate differences in distributions and abundances of lipid species across and within single cell types. Of note are distinct localizations of signals within specific layers of the macula. For example, phosphatidylethanolamine and phosphatidylinositol lipids were localized to central RPE cells, whereas specific plasmalogen lipids were localized to cells of the perifoveal RPE and Henle fiber layer. Subcellular compartments of photoreceptors were distinguished by PE(20:0_22:5) in the outer nuclear layer, PE(18:0_22:6) in outer and inner segments, and cardiolipin CL(70:5) in the mitochondria-rich inner segments. Several lipids, differing by a single double bond, have markedly different distributions between the central fovea and the ganglion cell and inner nuclear layers. A lipid atlas, initiated in this study, can serve as a reference database for future examination of diseased tissues.

This study revealed the presence of overage of latanoprost in some generic formulations and formation of degradation products. Packaging with gas tight containers may be one of the important factors for latanoprost stability, along with its storage at low temperature during patient usage.

Little is known about the neutralizing antibodies induced in HIV-1 patients on antiretroviral treatment, which constitute an interesting group of individuals with improved B cell profile. Plasma samples from 34 HIV-1 seropositive antiretroviral drug treated (ART) patients were tested for neutralization against a panel of 14 subtype-A, B and C tier 1 and tier 2 viruses in TZM-bl assay. Of the 34 plasma samples, remarkably all the plasma samples were able to neutralize at least one virus while 32 (94 %) were found to neutralize ≥50 % viruses tested. In terms of overall neutralization frequency, approximately 86 %, 68 % and 17 % of the virus/plasma combinations showed 50 % neutralizing activity at 1 > 60, 1 ≥ 200 and 1 ≥ 2000 dilutions respectively. The improvement in neutralizing activity was shown to be associated with ART in two follow up patients. The neutralization of viruses by two representative plasma samples, AIIMS221 and AIIMS265, was exclusively mediated by immunoglobulin G fractions independent of ART drugs and IgG retained cross-reactive binding to recombinant gp120 proteins. We observed a positive trend of neutralization with duration of ART (p = 0.06), however no such correlation was found with clinical and immunological variables like CD4 count (p = 0.35), viral load (p = 0.09) and plasma total IgG (p = 0.46). Our study suggests that the plasma antibodies from ART patients display high neutralizing activity most likely due to an improved B cell function induced by ART despite low antigenic stimulation.

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