creatine

# Introduction Retinal ganglion cells (RGCs) are the neurons that send visual signals from the eye to the brain. They rely on a **high-energy metabolism** because they must maintain electrical signals over long distances. In glaucoma and related optic neuropathies, elevated intraocular pressure (IOP) or poor blood flow can stress RGCs by limiting oxygen and nutrients. Emerging evidence suggests that RGCs under pressure-induced stress suffer early energy failure – their ATP levels drop before any visible cell loss ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC5371671/#:~:text=suggested%20that%20both%20IOP%20and,degeneration%20and%20preserve%20visual%20function)). Thus, therapies that boost cellular energy might protect RGCs from degeneration. One candidate is **creatine**, a compound cells use to buffer energy. This article reviews how creatine and its high-energy form *phosphocreatine (PCr)* support RGCs under stress, and what this could mean for glaucoma and aging. ## The Creatine–Phosphocreatine Energy Buffer **Creatine** is a natural molecule made in the liver, kidney and pancreas (from arginine, glycine, methionine) and stored mostly in muscle (≈95%) and also in brain and other tissues ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC4304302/#:~:text=Nearly%2095,ATP%20is%20regenerated%20using%20the)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12272710/#:~:text=The%20total%20creatine%20pool%20,increases%20blood%2C%20muscle%2C%20and)). Inside cells, creatine is converted back and forth to **phosphocreatine (PCr)** by the enzyme creatine kinase (CK). This *PCr–CREATINE system* serves as an **energy buffer**: when ATP is used up quickly (for example during muscle contraction or neuron signaling), PCr donates its phosphate to adenosine diphosphate (ADP) to reform ATP. Simply put, PCr can regenerate ATP far more quickly than mitochondria alone ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC4304302/#:~:text=Within%20just%20a%20few%20seconds%2C,for%20future%20muscle%20contraction%20use)). In practical terms, within a few seconds of intense activity, a resting cell’s ATP is depleted, but the CK system steps in by converting PCr back to ATP to keep energy levels stable ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC4304302/#:~:text=Within%20just%20a%20few%20seconds%2C,for%20future%20muscle%20contraction%20use)). After the burst of activity, excess ATP can again recharge creatine back into PCr for the next cycle. This reversible cycle makes creatine/PCr a “ready reserve” of energy, especially important in cells with high and rapid energy needs ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC4304302/#:~:text=Within%20just%20a%20few%20seconds%2C,for%20future%20muscle%20contraction%20use)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC5371671/#:~:text=ischemia,was%20independent%20of%20glial%20cells)). Importantly, this syst

Creatine and Energy Buffering in Retinal and Optic Nerve Tissues

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