Senior man holding an illuminated magnifying glass he uses to help him read because he suffers from Wet Macular Degeneration.

Macular Degeneration Studies With Peptide P21

In age-related macular degeneration (AMD), the macula—a tiny core region of the retina responsible for regulating eye focus—degenerates.

AMD causes the majority of eyesight loss. The irreversible destruction of the macula in AMD causes vision loss needed to see in color.

Researchers report the occurrence of AMD pathology and its prevention by chronic presentation with the neurotrophic peptidergic compound P021 in aged rats and 3xTg-AD mice.

Senior man holding an illuminated magnifying glass he uses to help him read because he suffers from Wet Macular Degeneration.

In the aged rats, scientists observed a rosette-like structure forming in addition to photoreceptor degeneration, vacuoles, lipofuscin granules, and atrophy in the retinal pigment epithelium (RPE).

Additionally, they discovered Bruch’s membrane (BM) thickening and vacuoles. In many layers of the retina, gliosis and astrogliosis were detected.

Furthermore, they discovered that the sub-retina of aged rats and 3xTg mice were abundant with total tau, phosphorylated tau, Aβ/APP, and VEFG.

Presentation of P021 for three months in rats and eighteen months in 3xTg mice appeared to improve the aforementioned pathological alterations.

These findings indicate the potential of P021 in the context of AMD and retinal changes associated with aging and Alzheimer’s disease.

P21 Peptide and Macular Degeneration Research

A dry version and a moist form of AMD exist. The majority of cases are of the dry, non-neovascular kind. The RPE, choriocapillaris, and photoreceptors all cause senescence as a result.

It is neovascular wet AMD. Scarring, bleeding, and vascular leakage result from new blood vessels penetrating Bruch’s membrane (BM) from the choroid.

Choroidal neovascularization (CNV) causes visual loss in wet AMD, which is less prevalent than in dry AMD. Researchers think that age-related macular tissue loss, pigment deposition in the macula, or both contribute to dry AMD.

Several unknown components likely contribute to the etiopathogenesis of AMD, making it a complex illness with many potential causes.

More and more evidence points to the immune system as a critical factor in the development of AMD by inducing neuroinflammation in the retina. Nutritional intervention may halt the development of AMD from its dry to its wet form. 

As a central nervous system component, the retina provides a direct view of brain disease. Neurons, astrocytes, microglia, and microvasculature are all present in the retina, like in the brain.

The two organs share many physiological functions and exhibit some of the same neurodegenerative alterations seen in Alzheimer’s disease. Research in Alzheimer’s disease may benefit from creating ocular biomarkers.

Amyloid-β (Aβ) and tau hyperphosphorylation are two parallels between Alzheimer’s disease (AD) and amyloid-beta (AMD), along with neurodegeneration and neuroinflammation. “AD of the eye” is another name for AMD.

P21 Peptide and the Eyes

In a prior study on the effects of long-term presentation of P21 on tau pathology and cognitive impairment in older rats and mice, researchers found no evidence of a decline in overall function due to P21, leading them to speculate that there are likely no other effects.

The loss of photoreceptor cells was measured by counting and evaluating the number of rows and thickness of ONL layers.

The findings imply rats between the ages of 22 and 24 months appeared to have significantly thinner ONL layers in both the central and peripheral retinas, as shown by H&E staining.

The investigations also purport that P21 seemed to have a greater impact on preventing these degenerative alterations in the central retina than in the peripheral retina.

The lack of a significant difference between 5 to 6 months old and 22 to 24 months old presented with P21 indicates that P21 may prevent ONL lesions.

It was hypothesized there may have been a noticeable trend toward increasing the number of rows in the peripheral retina of the 22- to 24-month-old/Veh rats compared to the 5- to 6-month-old/Veh rats and the thickness of the INL in the peripheral retina was also decreased in these rats.

Furthermore, researchers suggested that outer retinal folds and rosette-like structures disrupted the laminar organization in the central retina of rats around 22 to 24 months old.

In these abnormalities, the nuclei of photoreceptor cells were organized in a semi-spherical pattern that invaded the inner nuclear layer (INL), spread over the outer plexiform layer (OPL), and occupied the outer nuclear layer (ONL).

The photoreceptor’s inner segment (IS) seemed to occupy the central position of the rosettes.

Scientists theorized that neither the 5- to 6-month-old/Veh rats nor the 22- to 24-month-old/P021 rats appeared to have aberrant structures similar to this.

These findings suggested photoreceptor cell degeneration in the central retina and inner nuclear layer degeneration in the peripheral retina in rats approximately 22 to 24 months old with vascular disease (Veh) mutation.

Additionally, it was suggested that rats approximately 19 to 21 months old seemed protected from AMD-like pathology in the central retina after a 3-month presentation with P21.

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[i] Liu, Yinghua, et al. “Inhibition of AMD-Like Pathology With a Neurotrophic Compound in Aged Rats and 3xTg-AD Mice.” Frontiers in Aging Neuroscience, vol. 11, 19 Nov. 2019, 10.3389/fnagi.2019.00309.

[ii] “Synthetic Peptide Outlasts Macular Degeneration Med Eylea in Animal Models.” FierceBiotech,

[iii] “Epitope Mapping – an overview | ScienceDirect Topics.” 

[iv] N. Baazaoui and K. Iqbal, “Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound,” Alzheimers Res. Ther., vol. 9, Jun. 2017, doi: 10.1186/s13195-017-0273-7. 

[v] B. Li et al., “Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice,” FEBS Lett., vol. 584, no. 15, pp. 3359– 3365, 2010, doi: 10.1016/j.febslet.2010.06.025.