Transformative Algal Interventions in Ophthalmology, Mechanisms, and Future Potential: A Review

ABSTRACT

Microalgae have become the focus of many studies concerning ocular health due to the varied chemical composition of algae. These organisms contain bioactive compounds especially carotenoids, polyunsaturated fatty acids (PUFAs), and antioxidants, which have proven beneficial in some diseases of the eyes. This review is focused on summarizing the potential therapeutic use of algae in treating eye diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR), and dry eye syndrome. We will also describe the pathways by which algae produce benefits, review cases of clinical studies, and explore future uses for algae in treatments.

INTRODUCTION

There can be more than 24 eye ailments that go along with the aging process and are regarded as a possible cause of blindness and vision loss including age-related macular degeneration (AMD), catarrh, glaucoma, and diabetes retinopathy. In its report of 2021, WHO established that, over 2 billion people globally have some form of visual impairment which is potentially avoidable or compelling; half of the affected population, being at the early stages of the condition.[1] According to Wong et al., these diseases are the culprits of the rising health system strain, not to mention the rise of economic facets in societies as people across the world continue to age.[2]

The diseases, lamda’m AMD with prediction with 196 million people affected worldwide by 2020 to 288 million by 2040 and age 50 years and above with irreversible blindness. In this regard, current types of cataracts in totality are the main reason for blindness at large; more than twenty million people are now blind by this alone.[3] Estimation in glaucoma with features of increasing intraocular pressure (IOP) and death of retinal ganglion cells (RGCs) projected that 74–80 million persons would be affected globally in the year 2040.[4] International Diabetes Federation estimates showed that approximately 463 million adults were living with diabetes in the year 2019; the number is expected to rise to nearly half a billion in the year 2045.[5]

The microalgae of importance are Chlorella, Spirulina, and Dunaliella, and the macroalgae are Laminaria and Ulva, which are essentially seaweed. These organisms have been sources of valuable bioactive compounds such as carotenoids, omega-3 fatty acids, structurally diverse polysaccharides, green fluorescent phycobiliproteins, and antioxidants, which have crucial roles in preventing or reducing organic ills from increased levels of oxidative stress, cellular inflammation, or injury, as features related to the pathogenesis of many ocular diseases described.[6]

The ROS can be toxic to Oxidative Stress (OE) in eye diseases, which if not regulated has the propensity to cause AMD and DR.[7] Furthermore, inflammation remains an important component of various diseases such as glaucoma, dry eye disease (DED), and DR; the pro-inflammatory cytokines enhance tissue invasion and disease progression.[8] It has been postulated that carotenoids originating from algae, mainly, lutein and zeaxanthin and omega-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that possess antioxidant/anti-inflammatory capacity may be of tremendous benefits in the protection of the eye, specifically the retina.[7,9]

In addition to antioxidative and anti-inflammatory effects, compounds, including phycocyanin and astaxanthin extracted from algae are beneficial for glaucoma and DR models that had progressive loss of retinal ganglion neurons and the optic nerve.[9,10] Moreover, Spirulina and Chlorella both have polysaccharides that can promote cell division apart from tissue repair which is extremely crucial in the treatment of ocular surface ulcers and corneal injury.[11]

The compounds have been shown, in both clinical and preclinical investigations, to moderate the progression of retinal degeneration, exhibit Ip lowering activity useful in glaucoma patients and stimulate tear secretion in individuals suffering from dry eye syndrome.[8,12]

The purpose of this review is to discuss the therapeutic possibilities of looking at compounds extracted from algae for major macular diseases such as AMD, glaucoma, DR, cataract, and dry eye.

MECHANISMS OF ACTION OF ALGAE IN OCULAR HEALTH

This mechanism is owing to a high concentration of bioactive compounds in algae that possess antioxidant stress reduction potential and neuroprotection in eye diseases. Table 1 shows the algal derived compounds and their effect on ocular health

Table 1.

Mechanisms of action of algae in ocular health

Mechanism	Algae-derived compounds	Proposed mechanisms in ocular health	References
Antioxidant activity	Carotenoids (lutein, zeaxanthin), astaxanthin, polyphenols	Neutralize reactive oxygen species and free radicals; protect retinal cells from oxidative stress	[2]
Anti-inflammatory effects	Omega-3 fatty acids (DHA, EPA), phycocyanin, astaxanthin	Reduce inflammation by modulating pro-inflammatory cytokines; inhibit inflammatory pathways in the retina and cornea	[8,6]
Neuroprotection	Phycocyanin, astaxanthin, omega-3 fatty acids	Protect retinal ganglion cells and neurons from apoptosis and degeneration	[6]
Cell regeneration and repair	Polysaccharides (e.g., carrageenan, agar), growth factors	Promote cellular regeneration and repair; improve wound healing in corneal and retinal tissues	[11]
Anti-apoptotic effects	Astaxanthin, phycocyanin	Inhibit apoptosis in retinal cells by activating survival signaling pathways	[6]
Vascular health and angiogenesis	Omega-3 fatty acids	Promote healthy blood vessel function, reduce retinal vascular leakage, and prevent retinal edema	[13]
Blue light filtering	Lutein, zeaxanthin	Absorb and filter harmful blue light, protecting the retina from photo-oxidative damage	[2]

Antioxidant activity

As it has been pointed out, algae are good sources of antioxidants, such as carotenoids—lutein and zeaxanthin, polyphenols, and phycobiliproteins. These antioxidants can assist in preventing oxidative stress which is a big cause of age-related illnesses of the eye such as AMD and cataracts.[6] Among them, carotenoids actively protect important retinal cells from reactive oxygen and filter out dangerous blue light.

Anti-inflammatory effects

Inflammation is the reason behind almost 50% of eye diseases, including DR, glaucoma, and DED. Compounds such as omega 3 fatty acids, DHA and EPA, from microalgae species like Nannochloropsis and Schizochytrium may help in minimizing inflammation in ocular tissues.[8]

Neuroprotection

Some algae, for instance, Spirulina and Chlorella have been raised for their neurotrophic properties which make them applicable where the optic nerve or cells of the retina are involved. Their biologically active sugars such as phycocyanin and peptides can contribute to retinal neurons saving against degeneration.[10]

Cell regeneration and repair

Some algae, for instance, green microalgae such as the Chlorella vulgaris have growth factors and polysaccharides which have reputed characteristics of cell development and renewal and can be used in eye disorders such as DR and corneal damage.[11]

ALGAE IN THE TREATMENT OF SPECIFIC EYE DISEASES

Algae-Derived Compounds such as Lutein, Zeaxanthin Astaxanthin, Omega-3 Fatty Acids and Phycocyanin are used to treat various eye disease like Glaucoma and Cataracts [Table 2].

Table 2.

Algae in the treatment of specific eye diseases

Eye disease	Algae-derived compounds	Mechanism of action	Clinical evidence and references
Age-related macular degeneration	Lutein, zeaxanthin (from Chlorella, Spirulina, Dunaliella)	Protect macular cells from oxidative stress; filter blue light; enhance macular pigment density	[2]
Glaucoma	Omega-3 fatty acids (DHA, EPA), astaxanthin	Reduce intraocular pressure; protect retinal ganglion cells from degeneration	[9]
Diabetic retinopathy	Astaxanthin, Omega-3 fatty acids, phycocyanin	Reduce oxidative stress and inflammation; protect retinal vasculature; inhibit angiogenesis	[13]
Cataracts	Lutein, zeaxanthin, astaxanthin	Prevent lens opacification through antioxidant action; protect lens cells from oxidative damage	[4]
Dry eye disease	Omega-3 fatty acids (DHA, EPA)	Improve tear production; reduce inflammation in the lacrimal glands and ocular surface	[8]
Retinal degeneration (e.g., retinitis pigmentosa)	Astaxanthin, phycocyanin	Protect retinal cells from apoptosis and oxidative damage; support retinal neuroprotection	[6,12]
Corneal repair and wound healing	Polysaccharides (e.g., agar, carrageenan), omega-3 fatty acids	Aid in corneal tissue regeneration and reduce inflammation at the ocular surface	[11]

Age-related macular degeneration

This is a deformity of the retina that majorly attacks aged people, and is considered to be a severe disease that affects the macula. Oxygen-induced stress, inflammation, and cell death for AMD are crucial elements in its formulation. Due to their ability to filter blue light and their antioxidant characteristics, algal carotenoids lutein and zeaxanthin have some potential to be inhibitors of AMD.

Lutein and zeaxanthin

These carotenoids which are widely available in algae such as Chlorella and Dunaliella salina are mainly located in the macula of the retina. Specific carotenoids called lutein and zeaxanthin have been demonstrated to enhance vision and decrease the worsening of AMD.[7]

Clinical evidence

Clinical evidence stated that when patients with AMD were supplemented with Spirulina, a blue green substance with a high content of carotenoid vitamins, it improved the condition of the macula and minimized the effect of oxidative stress.[14]

Glaucoma

One of the leading causes of blindness, a disease called glaucoma includes optic nerve head damage best with vision loss. IOP is still one of the greatest predictors of glaucoma. DHA and EPA derived from algae have also demonstrated a potential to reduce IOP and protect RGCs from damage.

Omega-3 fatty acids

Nannochloropsis, for instance, contains omega-3 essential fatty acids that work on cutting inflammation and enhancing the quality of blood vessels in the eye. Supplementation with omega-3 fatty acids has been reported to have a protective effect on the retina and optic nerve.[12]

Clinical evidence

Clinical trials are still in early stages, but some studies have indicated that omega-3 supplementation may be beneficial for glaucoma patients by reducing IOP and preventing optic nerve damage.[12]

Diabetic retinopathy

DR is a major cause of vision loss in diabetic patients. It refers to damage caused by prolonged hyperglycemia to the retina leading to tissue inflammation, development of microaneurysm, and cell death. Phyllotaurin isolated from red algae has proven promising beneficial properties in experimental models of DR, including antioxidants astaxanthin and omega-3 PUFAs.[12]

Astaxanthin

Derived from red microalgae such as Haematococcus pluvialis, astaxanthin is a powerful antioxidant that has shown potential in preventing retinal damage in DR. It reduces oxidative stress and inflammation, thereby protecting retinal cells (Wang et al., 2012).

Omega-3 fatty acids

As mentioned earlier, omega-3s also play a role in reducing inflammation and improving retinal health in diabetic individuals. Omega-3 supplementation has been proposed to prevent the progression of DR.[9]

Cataracts

Carotene, lutein, and zeaxanthin derived from algae are also believed to prevent cataract diseases and in addition, delay the formation of cataracts.

Carotenoid protection

It has been found that lutein and zeaxanthin which are a class of carotenoids have antioxidant effects thus preventing iatrogenic changes in the lens and consequently cataract formation.[13]

Dry eye disease

DED is therefore described as any inflammatory disease of the ocular surface as a consequence of tear deficiency, which is an interaction of the precorneal tear film and the underlying ocular surface. In particular, algae-based omega-3 fatty acids DHA and EPA may be helpful in DED because they improve tear production and reduce inflammation.

Omega-3 fatty acids

Omega-3s are believed to support the stability of the tear layer and decrease inflammation in cases of DED. According to research proposed, omega-3 fatty acid-rich algae-derived DHA and EPA positively impact aspects of dry eye.[8]

CLINICAL STUDIES AND APPLICATIONS

The clinical research experiments have been made to evaluate the effectiveness of various compounds obtained from algae when applied to eye diseases. These studies have looked at antioxidant nutrients that include lutein and zeaxanthin as well as astaxanthin and omega-3 PUFAs.

Study on lutein and zeaxanthin

Another clinical trial by Amin et al. investigated the effect of lutein and zeaxanthin from Spirulina in patients with early AMD and the result showed the improvement of the visual function and macular pigment density.[15]

Omega-3 supplementation

A study by López and Müller showed that omega-3 supplementation from algae-based sources helped reduce IOP in glaucoma patients and improved retinal health.[12]

CONCLUSION AND FUTURE DIRECTIONS

Organic compounds present in algae including carotenoids (lutein and zeaxanthin), omega-3 PUFAs (DHA, EPA), and antioxidants (astaxanthin) exhibit great potential to positively influence oxidative stress, inflammation, and cell health and repair in different ocular tissues.[9,10,12] These mechanisms are especially important if we consider prevalent and very often chronic diseases in aging eyes such as AMD, glaucoma, DR, cataract, and DED.[11,12]

Health benefits that have shown some positive results include using algae constituents to enhance the health of the retina and prevent macular degeneration, decrease IOP in glaucoma-afflicted individuals, and promote tear secretion in patients diagnosed with dry eye.[8,12]

Nevertheless, the plant research findings present some challenges that would hinder the total harnessing of the efficacy of algae in ocular health.[7] Current clinical trials have revealed positive effects of cytokine release syndrome (CRS), but most such trials are flawed by methodological problems such as a small number of subjects, short experimental period, and diverse use of treatment protocols.[15] Consequently, there exists a major gap in large-scale, methodologically sound human studies that evaluate the safety of algae-derived compounds for the treatment of chronic ocular disorders, including AMD, glaucoma, and DR, as well as the appropriate dosage regimen in these conditions.[10]

FUTURE DIRECTIONS

Large-scale clinical trials

A majority of clinical studies encountered are small sample size studies with relatively low statistical significance. To prove that algae-based therapies are effective in the management of ocular diseases, large clinical trials, preferably multicenter RCT are required.

Mechanistic studies

Further research should be directed towards establishing an understanding of the cellular mechanisms these algae may directly affect, like Nrf2 signaling which is associated with oxidative stress, or NF–κB signaling which involves inflammation and may help in designing algae-based therapy with respect to the specific ocular pathology present.[9]

Standardization of algae-based formulations

There are a few issues that are important for the next steps in the use of treatments derived from algae: first, most of the mentioned products are too different in composition and are not unified enough.

Combination therapies

Since many ocular diseases are intricate and multifactorial in etiology, further investigations could compare the additive effects of some of these algae-derived compounds with conventional therapies. For instance, supplementing omega-3 fatty acids derived from algae together with anti-VEGF in AMD, or astaxanthin with topical steroids in DED could show better clinical efficacy.[8]

Personalized approaches

The research area of nutrigenomics (the science of analyzing genetic profiles and diet components) may promote the creation of individual algae nutrients corresponding to the risk profile of developing ocular diseases.[10]

Exploring algae from understudied species

Finding new phycobiliproteins, polyphenols, and phytochemicals’ eye-specific effects may enrich the pharmacopeia of natural remedies for the treatment of many ocular diseases.[6]

Multiple approaches are clearly supported where the unique nutrients of algae such as carotenoids, omega-3 fatty acids, antioxidants, and polysaccharides may help to prevent and control oxidative damage, inflammation, and retinal cell death.[1,4] Nevertheless, additional pharmacological investigation is essential for confirming the effectiveness and safety of these substances for human use, particularly by employing large-scale trending studies, determination of the molecular function, and definition of the formulation protocols.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.