Eyeworld Supplements

JULY 2021 | WHITE PAPER | 2 Sponsored by Regener-Eyes ® number of bioactive factors (lipids, proteins, enzymes, cytokines, chemokines, immunoregula- tory proteins, trophic and growth factors), as well as microRNAs (miRNAs), which, due to their tro- phic and antimicrobial properties, support normal fetal growth and offer protection against patho- gens and toxins. 10 Additionally, these placental biomaterials contain AF-MSC-sourced exosomes (AF-MSC-Exos), nano-sized extracellular vesicles that are enriched with AF-MSC-derived immu- nosuppressive molecules and growth factors. 10–11 Due to their nano-sized dimensions and lipid en- velope, AF-MSC-Exos avoid biological barriers, and easily penetrate through the lipid-containing cell membranes of the ocular surface through di- rect fusion with the plasma membrane, thereby delivering their content to the cytosol of target cells. 10–12 Regener-Eyes ® is an engineered biological product derived from human placental-based biomaterials, manufactured under current Good Manufacturing Practices (cGMP), regulated and reviewed by the Food and Drug Administration (FDA). 9 Regener-Eyes ® incorporates Regenerative Processing Plant's (RPP) proprietary patented sterilization process to provide for a safe, sterile product for clinical use. 9 Regener-Eyes ® is en- riched with AF-MSC-Exos containing AF-MSC-de- rived immunoregulatory, angio-modulatory and trophic factors capable of bypassing biological barriers to efficiently attenuate ongoing inflam- mation, promoting enhanced tissue repair and regeneration. 8 Specifically, Regener-Eyes ® con- tains interleukin 1 receptor antagonist (IL-1Ra), soluble receptors of tumor necrosis factor alpha eye. 3–6 The administration of immunosuppressive eye drops has the potential to attenuate the on- going inflammation, resulting in the alleviation, as the well-developed protective mechanisms of the ocular surface ensure their rapid clearance from the pre-corneal tear film, thus limiting oc- ular penetration of the drug. 8 Therefore, there is a large unmet need for the development and clinical use of eye drops containing immunomod- ulatory factors that are able to bypass the ocular surface barrier and reach the target cells of the ocular surface and lacrimal system. 8 In line with these findings, Dr. Harrell re- cently developed Regener-Eyes ® (generic name "derived-Multiple Allogeneic Proteins Paracrine Signaling [d-MAPPS]"), an ophthalmic solution that contains a large number of immunoregula- tory factors that are capable of penetrating the ocular surface to efficiently attenuate the eye's detrimental immune response, which may help to promote the repair and regeneration of damaged corneal tissue. 9 Herein, we described in detail the molecular mechanisms and signaling pathways that are responsible for the immunomodulatory effects of Regener-Eyes ® , exploring the therapeu- tic potential of Regener-Eyes ® in the treatment of DED. Molecular mechanisms responsible for beneficial effects of Regener-Eyes ® in DED treatment Although Regener-Eyes ® is acellular, it contains proteins, cytokines in addition to the water, glucose, lactates and electrolytes, and placen- tal-derived biomaterials, which produce a large continued on page 3

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