Scientists tested three fat‑linked dopamine molecules (PALDA, OLDA, NADA) and found they can stop eye cells from turning into scar‑forming cells in lab dishes, but this work is early‑stage and only about eye disease, not general health or longevity.

Aberrant wound healing in the retina can manifest as proliferative vitreoretinopathy (PVR), which involves the myofibroblast transdifferentiation of retinal pigment epithelial (RPE) cells. In this study, experiments were conducted to examine the structure-activity relationships of endocannabinoid-like compounds, <i>N</i>-acyl dopamines, on the myofibroblast transdifferentiation of RPE cells. The collagen matrix contraction assay was used to assess myofibroblast function. Western blot analysis and immunocytochemistry techniques were used to evaluate myofibroblast markers. <i>N</i>-palmitoyl dopamine (PALDA), <i>N</i>-oleoyl dopamine (OLDA), and <i>N</i>-arachidonoyl dopamine (NADA), in a concentration-dependent manner, inhibited contraction of collagen matrices mediated by either primary porcine RPE cells treated with TGF-&#x3b2;2, or human RPE cells treated with TGF-&#x3b2;2 plus TNF&#x3b1; (TNT). The rank order of potency was PLDA = OLDA &gt; NADA. In contrast, the substitution of dopamine with other polar head groups led to a complete loss of their ability to inhibit myofibroblast transdifferentiation. Western blot analysis demonstrated that PALDA, OLDA, and NADA down-regulated the myofibroblast markers fibronectin and &#x3b1;-SMA. Immunocytochemistry experiments showed that these <i>N</i>-acyl dopamines reduced the incorporation of &#x3b1;-SMA into F-actin stress fibers. Overall, these structure-activity relationship studies demonstrate that the dopamine head group is crucial for <i>N</i>-acyl dopamine to inhibit myofibroblast transdifferentiation of RPE cell, whereas the fatty acid side chain determines the potency of it. This study points to the potential of <i>N</i>-acyl dopamines as a novel class of therapeutic agents for treating retinal fibrotic conditions, such as PVR.