What Nicotinamide Riboside Is Doing Inside Your Retina

You have probably heard about nicotinamide riboside. Maybe from a longevity podcast. Maybe because a friend started taking it for energy, or because you read something about NAD+ declining with age.

What almost no one in those conversations mentions: your retina may be the organ that needs NAD+ the most.

Two studies published in late 2024 and early 2025 looked specifically at what nicotinamide riboside does inside retinal tissue. The findings are notable, and they are directly relevant to anyone thinking seriously about long-term eye health.

Here is what the research actually shows.

Why Your Retina Runs on NAD+

Nicotinamide riboside, or NR, is a form of vitamin B3. Your cells use it to produce NAD+ (nicotinamide adenine dinucleotide), a molecule that sits at the center of cellular energy production. NAD+ helps the mitochondria in your cells generate ATP, the fuel that keeps everything running.

That matters everywhere in the body. But it matters most in tissues with the highest energy demands. And at the top of that list is the retina.

The retina has the highest mitochondrial density of any tissue in the human body. Your photoreceptors, the rods and cones that detect light, pack more mitochondria per cell than nearly any other cell type. They need constant, enormous amounts of energy to perform phototransduction, the process of converting light into electrical signals, from the moment you wake up to the moment you fall asleep.

The problem: NAD+ levels decline with age throughout the body, and the retina is no exception. As that decline accelerates, retinal cells face two simultaneous crises. Energy production slows. And the cellular defense systems that depend on NAD+ begin to fail. If you want to go deeper on the science behind NAD+ and cellular energy in the eye, the Our Science page covers the full mechanism.

What the 2025 IOVS Study Found: A New Mechanism

A study published in Investigative Ophthalmology and Visual Science in April 2025 identified something researchers had not previously mapped in retinal tissue: NR appears to suppress a specific inflammatory cascade that triggers retinal cell death.

Here is the mechanism. When retinal cells are stressed, their mitochondria can become damaged and begin leaking fragmented DNA into the cell's interior. The cell recognizes this DNA as a signal of injury and activates an inflammatory alarm called the cGAS-STING pathway. Once activated, STING triggers a process called pyroptosis, a particularly damaging form of inflammatory cell death. It is not quiet. It ruptures the cell and releases inflammatory signals that damage neighboring cells as well.

The study found that NR interrupted this cascade at the mitochondrial level. NR treatment preserved mitochondrial biosynthesis in retinal cells, reduced the amount of damaged DNA being released, and suppressed STING expression in reactive microglia, the immune cells of the retina that amplify the inflammatory response when activated.

In practical terms: NR appeared to calm the alarm system before it could trigger widespread cell death.

This was a laboratory study using a light-induced retinal degeneration model in mice, not a human trial. The mechanism it describes is real and specific, but the translation to human retinal disease requires careful interpretation.

What the Glaucoma Mouse Study Found: Retinal Ganglion Cell Protection

The second study, published in December 2024, took a different approach. Rather than mapping a mechanism in the lab, it tested oral NR supplementation directly in a mouse model of inherited glaucoma, a model that closely mirrors the pattern of optic nerve damage seen in human glaucoma.

The researchers used DBA/2J mice, which develop age-related elevated intraocular pressure and progressive retinal ganglion cell loss over time, the same pattern of neurodegeneration that defines glaucoma in humans. They gave mice oral NR starting at either four or nine months of age and continued through 12 months.

The results were significant. In the high-dose NR group, retinal ganglion cell counts averaged 1,412 cells per field. In the untreated control group, that number fell to 475 cells per field. That is a difference of roughly three times as many surviving neurons (p < 0.00001). Axon counts showed a similar pattern: 23,990 in the NR high-dose group versus 8,573 in controls (p < 0.0001).

NR treatment also delayed the elevation of intraocular pressure and prevented iris atrophy in this model, suggesting that NAD+ supplementation may have broader effects on the anterior segment of the eye as well.

Again, these are animal findings. The DBA/2J model is well-validated and widely used in glaucoma research, but mouse data and human outcomes are not the same thing. The researchers note that the parallels between this model and human pigment dispersion glaucoma make NR worth exploring as a therapeutic candidate in human disease.

Here Is Where You Pump the Brakes

Both studies are animal and laboratory research. No large-scale human randomized controlled trial has yet tested NR specifically for retinal protection or glaucoma neuroprotection in humans.

What does exist in humans is a body of research on nicotinamide, a closely related NAD+ precursor, including a Phase 2 trial at Columbia University that showed visual field improvements in 32 glaucoma patients, and the formal nicotinamide position statement the AGS and AAO issued in 2025. If you have not read it, we covered the AGS and AAO statement in detail, including what it does and does not recommend, in our breakdown of the nicotinamide research we covered when the AAO issued its formal position statement.

NR and nicotinamide are not the same molecule, and they have different bioavailability profiles and metabolic fates. Researchers are actively investigating whether NR's distinct pharmacokinetics make it more or less effective than nicotinamide for retinal tissue specifically. A randomized controlled trial of NR for glaucoma neuroprotection is currently registered and in progress.

The honest summary: the mechanism is real, the animal data is compelling, and the human trial data is still being built.

What Does This Mean for You?

If you are thinking about long-term retinal health and already familiar with the NAD+ story, these studies add meaningful specificity to what we know about NR in eye tissue. The STING pathway finding in particular identifies a mechanism that is directly relevant to the kind of chronic, low-grade retinal inflammation that accumulates with age.

If you have glaucoma or are at elevated risk, these findings are not a reason to skip your eye pressure management or stop working with your ophthalmologist. They are early evidence that NR may support the retinal ganglion cells most at risk in glaucoma through a different pathway than pressure reduction. Talk to your eye doctor about whether NAD+ supplementation makes sense as a complementary part of your approach.

For people who want to support their cellular energy and optic nerve health as part of a proactive, long-term approach, Sight Guard was formulated around this research. Sight Guard's lead ingredient is 300mg of nicotinamide riboside per serving, alongside four other ingredients that support cellular energy and antioxidant defense in the eye.

The Bigger Picture

These two studies are part of a growing body of work on NAD+ biology and the aging eye. The pattern emerging is consistent: retinal cells are among the most metabolically demanding and NAD+-dependent cells in the body, and they are among the most sensitive to NAD+ decline.

It is worth noting that NR is not the only cellular energy ingredient with a body of research behind it in retinal tissue. CoQ10, also present in Sight Guard, has its own established role in mitochondrial function and antioxidant defense in retinal cells. We covered what the research shows about what CoQ10 does for your retina in an earlier post.

The emerging picture is that the aging retina faces an energy deficit and an inflammatory burden simultaneously, and that these two problems are connected at the mitochondrial level. Understanding that connection is where the most interesting new eye health research is happening right now.

References

1. Zhu S, Zhang L, Tong P, Chen J, Wang C, Wang Z, Liu J, Duan P, Jiang Q, Zhou Y, Tan G, Zhang X, Jiang B. Nicotinamide Riboside Mitigates Retinal Degeneration by Suppressing Damaged DNA-Stimulated Microglial Activation and STING-Mediated Pyroptosis. Investigative Ophthalmology and Visual Science. 2025;66(4):14. DOI: 10.1167/iovs.66.4.14. PMID: 40192637.
2. Zhang N, Li Y, Zhang X, Chrenek MA, Wang J, Girardot PE, Sellers JT, Brenner C, Cui X, Geisert EE, Nickerson J, Boatright JH. Oral supplementation with Nicotinamide Riboside treatment protects RGCs in DBA/2J mouse model. PMC11642848. PMID: 39677633. Published December 2024. DOI: 10.1101/2024.12.03.626460.
3. DeParis SW, Oke I, Gaier ED, et al. American Glaucoma Society and American Academy of Ophthalmology Position Statement on Nicotinamide Use for Glaucoma Neuroprotection, 2025. Ophthalmology.
4. Williams PA, Harder JM, Foxworth NE, et al. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science. 2017;355(6326):756-760. DOI: 10.1126/science.aal0092. (Prior foundational NAD+ and glaucoma research.)