Normoftal

Normoftal is a short synthetic peptide targeting retinal cells to improve protein synthesis, protect against oxidative/inflammatory damage, and promote repair. Used to support vision in glaucoma, diabetic retinopathy, and AMD.

- Experience early macular degeneration or diabetic retinopathy

- Seek retinal protection and slowed ocular aging

Mechanism of Action

How this peptide works in the body

Chromatin Remodeling and Gene Activation

Normoftal interacts with chromatin in retinal cells by disrupting tight nucleosome packaging, particularly via acetylation of histone H3 at lysine 9 and lysine 27 (H3K9ac, H3K27ac), while reducing repressive marks such as H3K9me3. This transition from heterochromatin to euchromatin opens promoter regions of genes related to retinal repair and cellular maintenance. RNA polymerase II recruitment is increased at loci encoding cytoskeletal proteins and synaptic scaffolds, crucial for visual signal transmission.

Epigenetic Modulation

This peptide promotes a transcriptionally active chromatin landscape by increasing p300/CBP-dependent histone acetyltransferase activity while repressing class I and II HDACs. It also shows potential to influence TET-mediated DNA hydroxymethylation, contributing to long-term gene reactivation. Normoftal may stabilize open chromatin via interaction with scaffold attachment regions (SARs), preserving access for transcription factors involved in neurotrophic signaling.

Neuroprotection and Synaptic Support

Normoftal enhances expression of brain-derived neurotrophic factor (BDNF) and synaptophysin through CREB-mediated transcription, aiding in retinal ganglion cell survival and synaptic plasticity. It maintains neurotransmitter balance by increasing vesicular glutamate transporter (VGLUT1) expression while suppressing excitotoxic NMDA receptor overactivation. Its impact on axon guidance proteins, such as GAP-43, supports regeneration of damaged retinal circuits.

Antioxidant Activity

Normoftal activates the Nrf2--ARE pathway by preventing KEAP1-mediated ubiquitination of Nrf2, thereby increasing transcription of antioxidant enzymes including SOD1, catalase, and glutathione peroxidase. It also upregulates thioredoxin reductase and peroxiredoxin systems, which play roles in detoxifying hydrogen peroxide and lipid peroxides in photoreceptors. Lys-Glu's acidic nature may directly chelate iron and copper ions, mitigating Fenton chemistry in the retina.

Anti-Inflammatory Effects

Normoftal reduces NF-κB activation in microglial and Müller glial cells, leading to decreased transcription of TNF-α, IL-1β, and IL-6. It suppresses COX-2 and iNOS expression in retinal pigment epithelial (RPE) cells, reducing prostaglandin and nitric oxide production. This mechanism helps prevent chronic low-grade inflammation that underlies age-related retinal degeneration.

Telomere Maintenance and Cellular Longevity

Early-stage studies indicate that Normoftal may upregulate TERT (telomerase reverse transcriptase) mRNA in RPE cells, potentially by alleviating epigenetic silencing at the TERT promoter. This activity helps preserve telomere length and replicative potential in retinal cells, contributing to tissue longevity and resistance to senescence-induced dysfunction.