Department of Pharmaceutical Sciences
University of Tennessee Health Science Center
Memphis, TN

BASIC RESEARCH PROJECT
CD5L-mediated Autophagocytosis in RPE cells

Research Interests
Scientific Summary:  Dr. Giorgianni has discovered that patients affected by an elderly eye disease, called age-related macular degeneration (AMD) that compromises their vision, have antibodies circulating in their blood that can attack and damage proteins present in the eye. One of these proteins, that may be targeted by the circulating antibodies, might be important for the removal of compounds toxic to the eye.

In Dr. Giorgianni’s proposed project, he will plan to carry out experiments to demonstrate the function of this protein, called CD5L, in the retinal pigment epithelium (RPE), a type of cell that is compromised in AMD patients. Dr. Giorgianni believes that CD5L functions as a carrier of toxic compounds, especially those derived from cholesterol, and that facilitates their degradation which in turn prevents their accumulation and resulting damage to the RPE.

Plans for 2021
Dr. Giorgianni proposes to continue his work begun in 2020 to determine the function of CD5L, a secreted glycoprotein, member of the scavenger receptor cysteine-rich (SRCR) super-family, in human RPE cells.  Recent data obtained by his laboratory show that ARPE-19 cells in the presence of recombinant human CD5L display a significant, time-dependent decrease in intracellular accumulation of OxLDL, which suggests activation of intracellular degradation processes.

Proposed experiments may confirm that the presence of CD5L inside the RPE cells accelerates the degradation of a compound, derived from cholesterol, called OxLDL.   The research team will also identify other proteins that are needed, together with CD5L, to degrade toxic OxLDL. For this part of the project, the laboratory will leverage their new analytical tools, including the mass spectrometer that can quickly identify and quantify proteins. The findings from the proposed experiments will help to better understand the cellular mechanisms that lead to AMD and could provide new leads for the development of new therapeutic strategies.

Specific Aims:
Aim 1: To determine the role of CD5L in RPE cells as a cytoprotective agent against OxLDL-mediated oxidative damage through facilitation of autophagocytosis
Aim 2: To characterize the molecular interactions between CD5L and other proteins that mediate the activation of autophagocytic processes.

Progress in 2020
Despite delays resulting from the coronavirus pandemic, Dr. Giorgianni’s progress findings were submitted to two publications, resulting in one manuscript publication in the International Journal of Molecular Sciences in November, 2020.  A second manuscript reporting on the proeomics studies was submitted in November, 2020.

2020 Publications