Eye drops may help patients with retinitis pigmentosa and dry age-related macular degeneration (AMD): but does Cord Blood Serum Drops also help??

Researchers at the National Institutes of Health (NIH) have developed eye drops containing short peptides derived from pigment epithelium-derived factor (PEDF), a natural protein that supports retinal cell health. These peptides, particularly the H105A variant, have shown promise in slowing vision loss in animal models of degenerative eye diseases such as retinitis pigmentosa and dry age-related macular degeneration (AMD). The study, published in Communications Medicine, led by Patricia Becerra, Ph.D., and Alexandra Bernardo-Colón, demonstrates that these peptides can penetrate the eye and reach the retina when applied as drops, reducing photoreceptor degeneration and preserving vision in mice without causing toxic side effects.

In mice bred to mimic retinitis pigmentosa, daily H105A eye drops retained up to 75% of photoreceptors during a critical week of cell loss, compared to near-total loss in placebo-treated mice. Remarkably, the preserved cells remained functional, responding to light, and were healthy enough to benefit from subsequent gene therapy, extending vision for six months. The peptides target cellular stress, a common factor in retinal diseases, offering a broad protective effect. Tests in a human retinal tissue model further confirmed the peptides’ ability to protect cells under stress, supporting potential human trials.

While these PEDF-based eye drops are not a cure, they could delay vision loss in various retinal conditions and complement gene therapies. The research, funded by the NEI Intramural Research Program and collaborators, marks a significant step toward clinical testing, leveraging PEDF’s natural role in combating retinal degeneration.

This research also prompted me to consider some of the drops we use to help severe dry eye patients. For instance, cord blood serum drops, PRP drops, and plasma rich in growth factor PRGF drops contain PEDF. If so, what percentage of these drops contains PEDF?

Here’s some of the information I found. None of the options mentioned above are FDA approved, but it does raise the intriguing possibility that using these drops may help, as suggested by the mechanism described in the research.

Also, as I discussed in a previous post regarding the below publication **on the use of cord blood serum drops to potentially help glaucoma patients, the mechanism described above could explain how cord blood serum drops could help heal nerve damage in glaucoma patients. However, these theories really need double-blinded, randomized control perspective studies to prove their efficacy. The risk is extremely low, though, as these drops are generally very safe if used properly and kept frozen or cold as indicated when they are distributed. All of these drops are preservative-free, so they must always be kept cold and used for about 5 to 7 days.

Which eye drop has the most amount of pigment epithelium-derived factor (PEDF): cord blood serum (CBS) drops, PRP eye drops, or PRGF eye drops?

To determine which of cord blood serum (CBS), platelet-rich plasma (PRP) drops, plasma rich in growth factors (PRGF), or autologous serum (AS) contains the most PEDF, we need to evaluate their composition, source, and how PEDF is likely preserved or concentrated in each. PEDF is a soluble glycoprotein present in human blood plasma/serum, produced by cells like hepatocytes and retinal pigment epithelium, not platelets. Its concentration in these preparations depends on the starting material (plasma or serum) and processing methods. 

Direct comparative studies measuring PEDF across all four drops are not available as far as I could find.

Overview of Each Preparation

1. Cord Blood Serum (CBS):
• Source: Derived from umbilical cord blood after clotting and centrifugation to remove cells, leaving serum rich in fetal growth factors and proteins.
• PEDF Presence: Contains PEDF as a natural plasma/serum component. Fetal blood may have unique PEDF levels due to developmental needs (e.g., regulating angiogenesis), but exact quantification is limited. Studies (e.g., Investigative Ophthalmology & Visual Science, 2015) on CBS eye drops imply PEDF is present, contributing to neurotrophic effects, though not precisely measured.
• Likely Concentration: Reflects fetal serum levels, potentially 3–16 µg/mL (adult range), but could be higher or lower depending on fetal physiology.
2. Platelet-Rich Plasma (PRP) Drops:
• Source: Whole blood centrifuged to concentrate platelets in plasma, retaining some plasma proteins.
• PEDF Presence: PEDF is in the plasma fraction (baseline ~5 µg/mL in adults per Biochemical Journal, 2003). Platelet activation releases growth factors (e.g., VEGF), but PEDF isn’t platelet-derived, so its level isn’t enhanced—likely stays at or below plasma baseline depending on plasma volume retained.
• Likely Concentration: Around 3–16 µg/mL (adult plasma range), possibly diluted if plasma is reduced in favor of platelet concentration.
3. Plasma Rich in Growth Factors (PRGF):
• Source: A specific PRP variant, often leukocyte-poor, prepared with a single centrifugation and calcium activation to release growth factors from platelets into plasma.
• PEDF Presence: Like PRP, PEDF comes from the plasma fraction, not platelets. PRGF retains plasma proteins similarly to PRP, but its focus on platelet-derived factors (e.g., PDGF, TGF-β) doesn’t concentrate PEDF. No evidence suggests PRGF alters PEDF levels beyond plasma norms.
• Likely Concentration: Comparable to PRP, ~3–16 µg/mL, depending on plasma content and preparation specifics.
4. Autologous Serum (AS):
• Source: Patient’s whole blood clotted and centrifuged to isolate serum, retaining all serum proteins without platelet enrichment.
• PEDF Presence: Contains PEDF as a native serum component, well-documented in ocular therapy studies (e.g., Current Eye Research, 2006). Adult serum levels are reported at 5–15 µg/mL (e.g., Journal of Clinical Endocrinology & Metabolism, 2006), varying with health status (e.g., elevated in metabolic syndrome).
• Likely Concentration: Consistently around 5–15 µg/mL in healthy adults, undiluted by processing since it’s pure serum.

Comparative Analysis

• Baseline PEDF Source: All four contain PEDF from plasma/serum, not platelets. CBS and AS are serum-based (post-clotting), while PRP and PRGF are plasma-based (pre-clotting, though activation may mimic serum partially). Serum typically has slightly higher protein concentrations than plasma due to clotting factor removal, but PEDF levels are similar between the two in unprocessed states.
• Processing Impact:
• CBS: Unaltered serum from cord blood, preserving all native proteins. Fetal PEDF levels are speculative but could be elevated for developmental roles (e.g., anti-angiogenesis), potentially exceeding adult norms.
• PRP: Plasma diluted or maintained depending on centrifugation (e.g., 1:1 to 1:4 plasma-to-platelet ratio). PEDF isn’t concentrated, so it’s likely at or below adult plasma levels (~5 µg/mL).
• PRGF: Similar to PRP, with plasma as the base. No evidence of PEDF enrichment; likely matches PRP levels (~5 µg/mL).
• AS: Pure serum, no dilution or concentration beyond natural levels. Reflects adult serum PEDF (~5–15 µg/mL), consistent across studies.
• Quantitative Data:
• Adult plasma/serum: 3–16 µg/mL (mean ~5–10 µg/mL).
• Fetal serum (CBS): Unknown precisely, but hypothesized to be in or above this range due to fetal growth factor richness (e.g., higher EGF, VEGF in CBS).
• PRP/PRGF: Likely 3–10 µg/mL, possibly lower if plasma is minimized.

Which Has the Most PEDF?

• Cord Blood Serum (CBS): Likely the highest. Its fetal origin suggests a potential for elevated PEDF to support developmental processes (e.g., neuroprotection, vascular regulation). While not directly quantified, CBS’s richness in trophic factors (e.g., 10–20x higher EGF than AS) hints at higher PEDF, possibly exceeding adult serum’s 15 µg/mL ceiling in some cases.
• Autologous Serum (AS): Strong contender, with reliable adult levels (5–15 µg/mL). It’s undiluted serum, so PEDF is fully retained, but it reflects adult physiology, not fetal enhancement.
• PRP and PRGF: Tie for lowest. Both are plasma-based, and PEDF isn’t concentrated by platelet activation. Levels likely match or fall below adult plasma (3–10 µg/mL), depending on plasma retention. PRGF’s leukocyte-poor nature doesn’t affect PEDF, making it equivalent to PRP here.

Critical Takeaway

CBS likely has the most PEDF due to its fetal origin and potential for developmentally elevated levels, though exact data is lacking. AS follows with consistent adult serum levels (5–15 µg/mL). PRP and PRGF have the least, as PEDF remains at or below plasma baseline (~5 µg/mL) without enrichment. Without a head-to-head study, CBS edges out based on its bioactive profile, but confirmation would require direct measurement (e.g., ELISA) of each preparation. If you’re choosing for PEDF-specific benefits (e.g., anti-angiogenesis), CBS or AS might be preferable over PRP/PRGF.

**NOTE THE BELOW IS LIMITED DATA: The primary evidence for CBS in glaucoma treatment comes from the 2018 case report by Campos et al., with other publications (reviews) referencing this study. No large-scale clinical trials are cited in the provided data.

• Ongoing Research: The clinical trial (NCT03609125) mentioned in the 2018 report may provide further insights, but results are not included in the provided information.

1. Publication: Topical Treatment with Cord Blood Serum in Glaucoma Patients: A Preliminary Report

• Source: Case Reports in Ophthalmological Medicine, 2018; Published July 25, 2018
• DOI: 10.1155/2018/2381296
• Authors:
• Emilio Campos
• Piera Versura
• Giuseppe Giannaccare
• Adriana Terzi
• Silvia Bisti
• Marina Buzzi
• Stella Di Marco
• Affiliations:
• Authors are primarily affiliated with institutions in Italy:
• Emilio Campos, Piera Versura, Giuseppe Giannaccare, and Marina Buzzi: Department of Specialized, Diagnostic and Experimental Medicine, Ophthalmology Unit, Alma Mater Studiorum University of Bologna, Bologna, Italy.
• Adriana Terzi: Department of Computer Science and Engineering, University of Bologna, Bologna, Italy.
• Silvia Bisti, Stella Di Marco: Department of Biotechnology and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy, and National Institute of Neuroscience, Milan, Italy.
• Details of the Work:
• Study Design: Case report and retrospective data analysis involving two patients with advanced glaucoma and ocular surface discomfort but no signs of keratopathy.
• Methodology: CBS eye drops, characterized for growth factor (GF) content, were administered topically for two months to relieve subjective ocular surface symptoms. Patients were monitored with intraocular pressure (IOP) controls and visual field tests.
• Findings: Retrospective analysis showed improvements in visual field parameters (Mean Deviation and Pattern Standard Deviation) after CBS treatment. An unexpected amelioration was observed in the contralateral untreated eye of one patient, suggesting possible inter-eye cross-talk.
• Preparation of CBS: Umbilical cord blood was collected from ex utero placenta vessels after informed consent, following guidelines by the Foundation for the Accreditation of Hematopoietic Cellular Therapy (FACT). Blood was clotted, centrifuged, frozen at -80°C, thawed, pooled, diluted by 20% in sterile PBS, filtered, and aliquoted into single-dose vials.
• Ongoing Research: The same group is conducting a non-randomized clinical study with a 4-month follow-up using topical CBS in glaucoma patients (ClinicalTrials.gov NCT03609125).
• Proposed Mechanism:
• CBS contains high levels of growth factors (e.g., TGF-α, b-NGF, PDGF-bb) known to promote corneal epithelial healing but also shown to exert neuroprotection in experimental glaucoma models.
• These growth factors may act synergistically to protect retinal ganglion cells (RGCs), which degenerate in glaucoma, potentially slowing disease progression.
• The neuroprotective action is hypothesized to address multifactorial neurodegenerative mechanisms in glaucoma, including neurotrophin deprivation, oxidative stress, glial activation, and mitochondrial dysfunction.
• The observed bilateral effect in one patient suggests possible systemic or neural cross-talk between eyes, though the exact mechanism remains speculative and requires further investigation.
• Limitations:
• The study is preliminary, based on only two patients, and described as a “serendipitous” finding.
• The improvement in visual fields may be partly due to alleviated ocular surface discomfort, which could enhance visual field test performance.
• Further prospective studies with larger cohorts are needed to confirm efficacy and mechanisms.

2. Publication: Umbilical Cord Blood and Serum for the Treatment of Ocular Diseases: A Comprehensive Review

• Source: Ophthalmology and Therapy, 2020; Published February 26, 2020
• DOI: Not specified in the provided results, but available via SpringerLink.
• Authors:
• Giuseppe Giannaccare
• Adriano Carnevali
• Carlotta Senni
• Vincenzo Scorcia
• Others not fully listed in the provided data.
• Affiliations:
• Authors are primarily from Italy:
• Giuseppe Giannaccare: Department of Specialized, Diagnostic and Experimental Medicine, Ophthalmology Unit, Alma Mater Studiorum University of Bologna, Bologna, Italy.
• Other authors are likely affiliated with Italian institutions, though specific affiliations for Carnevali, Senni, and Scorcia are not detailed in the provided results.
• Details of the Work:
• Study Design: A comprehensive review of blood-derived products, including umbilical cord blood serum (UCBS), for treating ocular diseases affecting the anterior and posterior segments of the eye.
• Focus on Glaucoma: The review references the preliminary study by Campos et al. (2018) on CBS use in glaucoma patients, noting positive results in visual field test parameters.
• Scope: Discusses the therapeutic potential of UCBS eye drops for various ocular conditions, including dry eye syndrome, corneal epithelial defects, and neurodegenerative disorders like glaucoma.
• Advantages of UCBS: UCBS allows collection of large serum volumes, is feasible for patients with poor health (e.g., anemia or blood dyscrasia), and contains high concentrations of biologically active components and growth factors.
• Proposed Mechanism:
• The efficacy in glaucoma is attributed to the high growth factor content in UCBS, which may exert a neuroprotective effect on the optic nerve and retinal ganglion cells.
• Growth factors in UCBS, such as neurotrophic factors, could mitigate neurodegenerative processes in glaucoma, including RGC death due to oxidative stress, neurotrophin deprivation, or excitotoxicity.
• The review emphasizes that these findings are preliminary and require further investigation to establish a causal link and detailed mechanisms.
• Limitations:
• The review relies on the limited data from Campos et al. (2018) for glaucoma-specific findings.
• No new primary data on glaucoma treatment with UCBS is presented; the discussion is based on existing literature.

3. Publication: Regenerative Therapy Using Umbilical Cord Serum

• Source: In Vivo, 2021; Published March 2021
• DOI: Not specified in the provided results.
• Authors: Not explicitly listed in the provided data, but the study is referenced in the context of regenerative medicine and ocular applications.
• Affiliations: Likely from Italy, based on the context of related studies and the focus on umbilical cord serum research in Italian institutions.
• Details of the Work:
• Study Design: A review article discussing regenerative medicine applications of umbilical cord serum (UCS), including its use in ocular diseases like glaucoma.
• Glaucoma Relevance: Mentions the use of UCS eye drops for treating glaucoma, alongside other conditions like severe dry eye, ocular burns, and neurotrophic keratitis.
• Therapeutic Context: UCS is highlighted as a rich source of growth factors, neurotrophic factors, and cytokines with anti-inflammatory, anti-apoptotic, and wound-healing properties.
• Applications: Beyond ocular use, UCS is combined with synthetic bio-scaffolds for tissue regeneration (e.g., tympanic membrane, bone, nerve).
• Proposed Mechanism:
• UCS contains higher levels of growth and neurotrophic factors compared to autologous serum, potentially enhancing neuroprotection in glaucoma by supporting RGC survival.
• The neuroprotective effects are linked to the presence of factors that promote cell proliferation, reduce inflammation, and counteract neurodegenerative processes like apoptosis.
• The mechanism is not fully elucidated but is thought to involve nourishing the ocular environment and supporting neural tissue repair.
• Limitations:
• The article is a review and does not present new experimental data on glaucoma.
• Specific details on glaucoma treatment outcomes are limited, and the reference to glaucoma is brief.

Summary of Mechanisms

The proposed mechanisms by which cord blood serum may help treat glaucoma include:

1. Neuroprotection via Growth Factors:
• CBS contains growth factors like TGF-α, b-NGF, and PDGF-bb, which have demonstrated neuroprotective effects in experimental glaucoma models. These factors may protect retinal ganglion cells from apoptosis, a hallmark of glaucoma.
• Neurotrophic factors in CBS could counteract neurotrophin deprivation, a key pathogenic mechanism in glaucoma.
2. Anti-inflammatory and Anti-apoptotic Effects:
• Cytokines and biologically active molecules in CBS may reduce inflammation and glial activation, which contribute to RGC death in glaucoma.
• Anti-apoptotic properties could help preserve RGCs and optic nerve integrity.
3. Support for Ocular Surface Health:
• By alleviating ocular surface discomfort, CBS may improve visual field test performance, indirectly benefiting glaucoma patients.
• Enhanced corneal epithelial health could support overall ocular function, potentially aiding in neuroprotection.
4. Potential Inter-eye Cross-talk:
• The unexpected improvement in the untreated contralateral eye suggests a possible systemic or neural cross-talk mechanism, though this is speculative and requires further study.
5. Addressing Multifactorial Pathogenesis:
• Glaucoma involves oxidative stress, mitochondrial dysfunction, and excitotoxicity. CBS’s broad spectrum of bioactive molecules may target multiple pathways, offering a holistic neuroprotective approach.