One of my amazing patients has been doing research on dry eyes for years. He has dry eyes and has been a wealth of knowledge on all the treatment options. As you have seen me write in the past, many eye surgeons do not know how to properly treat dry eye mostly because they are surgeons and are trained to do surgery, not necessarily treat the common medical malady of dry eye or chronic eye pain.

The information sheds light on a whole new category of medications that might help with dry eye symptoms.

Here are some facts.
1. PPARγ appears to regulate meibocyte differentiation and lipid synthesis (production of fat/meibum).
2. There are PPARγ receptors in monkey and human meibomian glands

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479436/

3. There are medications that stimulate these receptors. Fenofibrate (Triglide, Fibricor, Lipofen, Antara, Fenoglide, and Trilipix) appears to be a stimulator of PPARγ receptors.
4. No one I can find has looked into whether patients on these medications have protection against Meibomian Gland Dysfunction.
5. We need to find out if these medications help.

6. If you are on such a medication or about to start this, please let us know to check your Meibography & OSDI scores & Schirmer’s test before you start and follow you over time.

SLC

. 2016 Oct;14(4):484-494.

doi: 10.1016/j.jtos.2016.08.001. Epub 2016 Aug 12.

PPARγ Regulates Mouse Meibocyte Differentiation and Lipid Synthesis

James V Jester 1, Eric Potma 2, Donald J Brown 3

Affiliations

1Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA. Electronic address: jjester@uci.edu.
2Department of Chemistry and Beckman Laser Institute, University of California, Irvine, Irvine, CA.
3Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA.

PMID: 27531629

PMCID: PMC5065777

DOI: 10.1016/j.jtos.2016.08.001

Abstract

Purpose: Previous reports suggest that age-related meibomian gland atrophy is associated with decreased expression of the lipid-sensitive nuclear receptor, PPARγ. The purpose of this study was to identify the role of PPARγ in modulating meibocyte lipid synthesis.

Methods: Cytoplasmic and nuclear fractions from meibomian glands of young (2M) and old (2Y) C57Bl6 mice were probed using antibodies specific for PPARγ. Mouse meibocytes were cultured, immortalized using a SV40 lentiviral vector, and evaluated for lipid synthesis using LipidTox staining and CARS/Raman microspectroscopy. Lipid synthesizing clones were tested for effects of PPARγ agonist, rosiglitazone, on lipid synthesis and PPARγ localization, post-translational modification and induction of PPARγ response genes.

Results: The cytoplasmic fraction in young mice contained both 50 and 72 kDa PPARγ bands that were absent or reduced by 75% in older mice, respectively. Cultured meibocytes produced neutral lipid containing equal amounts of wax and cholesterol esters, similar to mouse meibum. Addition of rosiglitazone (10-50 μM) significantly increased lipid production (P<.05) in meibocytes, associated with SUMO1 sumoylation and cytoplasmic accumulation of the 72 kDa PPARγ. Rosiglitazone also increased the localization of PPARγ to the cytoplasm and up-regulated of PPARγ, ADP and ADFP mRNA.

Conclusions: This study confirms the loss of cytoplasmic/vesicular PPARγ localization in older, atrophic mouse meibomian glands. Furthermore, PPARγ stimulates lipid synthesis in mouse meibocytes, associated with PPARγ sumoylation and translocation to the cytoplasm. Taken together these data suggest that lipid synthesis in older mice is down regulated by a PPARγ mediated pathway.

Keywords: PPARγ; eyelid; lipid; meibocytes; meibomian gland; tear film.