Kai Kaarniranta

University of Eastern Finland | UEF · Department of Ophthalmology

Purpose: Apolipoprotein E4 (APOE4), a known risk factor for Alzheimer's disease, has controversially been associated with reduced risk of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). Here, we sought to systematically quantify the associations of APOE haplotypes with age-related ocular diseases and to assess their s...

Age-related macular degeneration (AMD) is a common eye disease among the elderly, which can result in impaired vision and irreversible loss of vision. The majority of patients suffer from the dry (also known as the atrophic) form of the disease, which is completely lacking an effective treatment. In the present study, we evaluated the potential of...

Introductory paragraph Age-related macular degeneration (AMD), the leading cause of geriatric blindness, is a multi-factorial disease with retinal-pigmented epithelial (RPE) cell dysfunction as a central pathogenic driver. With RPE degeneration, lysosomal function is a core process that is disrupted. Transcription factors EB/E3 (TFEB/E3) tightly co...

Age-related macular degeneration (AMD) is a largely incurable disease and an emerging problem in aging societies. It occurs in two forms, dry and wet (exudative, neovascular), which may cause legal blindness and sight loss. Currently, there is not any effective treatment for dry AMD. Meanwhile, repeated intravitreal injections with antibodies effec...

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1a protein and nuclear factor erythroid 2 like 2 (NFE2L2) gene, showed some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvemen...

The aim of the study was to investigate oxidative stress as well as cellular protein accumulation in corneal diseases including keratoconus (KC), macular corneal dystrophy (MCD), and Fuchs endothelial corneal dystrophy (FECD) at their primary affecting sites. Corneal buttons from KC, MCD, and FECD patients, as well as healthy controls, were analyze...

Increased oxidative stress, dysfunctional cellular clearance, and chronic inflammation are associated with age-related macular degeneration (AMD). Prolyl oligopeptidase (PREP) is a serine protease that has numerous cellular functions, including the regulation of oxidative stress, protein aggregation, and inflammation. PREP inhibition by KYP-2047 (4...

Degeneration and/or dysfunction of retinal pigment epithelium (RPE) is generally detected as the formation of intra- and extracellular protein aggregates, called lipofuscin and drusen, respectively, in patients with age-related macular degeneration (AMD), the leading cause of blindness in the elderly population. These clinical hallmarks are linked...

Importance: Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases. Objective: To identify novel genetic...

The retinal pigment epithelial (RPE) cell monolayer forms the outer blood-retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of RPE secondary cell...

Age-related macular degeneration (AMD) is an ever-increasing, insidious disease which reduces the quality of life of millions of elderly people around the world. AMD is characterised by damage to the retinal pigment epithelium (RPE) in the macula region of the retina. The origins of this multi-factorial disease are complex and still not fully under...

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is we...

References: Antioxidant systems are essential in many elderly diseases, including age-related macular degeneration (AMD). Oxidative stress, inflammation, protein degradation impairment, are well-described in AMD retinal pigment epithelial (RPE) cells. Nrf2 (NF-E2-related factor 2), master regulator of antioxidant defence, is linked to AMD, autophag...

Purpose: Since RPE cells has important regulatory role in retinal inflammation, we examined the secretion kinetics of proinflammatory cytokine IL-1b. Methods: IL-1β production and release from IL-1a-primed (4 ng/ml) ARPE-19 cells was induced by inhibiting proteasomal clearance and autophagy using MG-132 (5 μM) and Bafilomycin A1 (BafA; 50 nM), resp...

Purpose: Age-related macular degeneration (AMD) presents a limited potential of experimental studies on the target tissue from AMD patients. Therefore, it is important to have a reliable experimental model to study AMD pathogenesis. We differentiated induced pluripotent stem cells (PSCs) derived from individuals suffering from wet AMD into retinal...

Purpose: Chronic oxidative stress, disturbed proteostasis and increased protein aggregation are key hallmarks in Alzheimer's disease and age-related macular degeneration pathology. In this study, we assessed the protein aggregation and secretory autophagy related biomarker changes in 5xFAD mice model expressing abundant levels of human beta-amyloid...

Purpose: Dysfunctional intracellular clearance is associated with various diseases, including age-related macular degeneration (AMD). Previously, we reported the inhibition of intracellular clearance by the non-selective proteasome inhibitor MG-132 resulted in oxidative stress-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome activ...

Purpose: Age-related macular degeneration (AMD) is a complex disease and the most common cause of blindness among the elderly in the Western world. Dysfunctional cellular clearance and increased oxidative stress are known to play a role in retinal pigment epithelial (RPE) cell death and dysfunction, which secondarily leads to photoreceptor degenera...

Purpose: Melanin in intracellular organelles, melanosomes, protects the retinal pigment epithelium from ultraviolet radiation and oxidative stress (OS). However, despite the role of OS in the development of age-related macular degeneration (AMD), the effect of pigmentation-related genes on the risk of AMD onset is unclear. Methods: Finnish wet AMD...

Purpose: Patients with wet age-related macular degeneration (wAMD) exhibit altered levels of genetic and epigenetic material in their systemic circulation. Cellular level processes related to autophagy and inflammation have previously been shown to associate with wAMD and its progression. Thus, measuring RNA levels in peripheral blood may help unde...

Introduction: Age-related macular degeneration (AMD) is an eye disease leading to vision loss with poorly known pathogenesis and limited therapeutic options. Degradative autophagy (DA) is impaired in AMD, but emerging evidence points to secretary autophagy (SA) as a key element in AMD pathogenesis. Areas covered: SA may cause the release of prot...

In dry age-related macular degeneration (AMD), inflammation plays a key role in disease pathogenesis. Innate immune cells such as microglia and neutrophils infiltrate the sub-retinal space (SRS) to induce chronic inflammation and AMD progression. But a major gap in our understanding is how these cells interact with each other in AMD. Here, we repor...

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population with a limited understanding of its pathogenesis and the number of patients are all the time increasing. AMD is classified into two main forms: dry and neovascular AMD (nAMD). Dry AMD is the most prevalent form (80–90%) of AMD cases. Neovascular...

Purpose: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if dietary supplementation alone or in combinations might delay the progression of any of the stages of AMD. Methods: A SR and meta-analysis identifying cohort studies and randomized...

Age-related macular degeneration is a complex eye disease with the retina as the target tissue and aging as per definition the most serious risk factor. However, the retina contains over 60 kinds of cells that form different structures, including the neuroretina and retinal pigment epithelium (RPE) which can age at different rates. Other establishe...

Background Excessive exposure of the skin to UV radiation (UVR) triggers a remodeling of the immune system and leads to the photoaging state which is reminiscent of chronological aging. Over 30 years ago, it was observed that UVR induced an immunosuppressive state which inhibited skin contact hypersensitivity. Methods Original and review articles...

Purpose: To evaluate the changes in visual impairment (VI) due to age-related macular degeneration (AMD) during the past 40 years and the impact of novel therapies at population level. Methods: In this nationwide register-based study, we assessed the incidence, prevalence, severity, and onset age of VI due to AMD based on the Finnish Register of...

Antioxidant systems play key roles in many elderly diseases, including age-related macular degeneration (AMD). Oxidative stress, autophagy impairment and inflammation are well-described in AMD, especially in retinal pigment epithelial (RPE) cells. The master regulator of antioxidant defense Nrf2 has been linked to AMD, autophagy and inflammation. I...

Purpose: To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME). Methods: This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of <3 years duration, ETDRS central subfield thickness ≥ 310 μm by SD-OCT, and ET...

Emerging evidence suggests that the intracellular clearance system plays a vital role in maintaining homeostasis and in regulating oxidative stress and inflammation in retinal pigment epithelium (RPE) cells. Dysfunctional proteasomes and autophagy in RPE cells have been associated with the pathogenesis of age-related macular degeneration. We have p...

In addition to hypoxia, inflammation is capable of inducing vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. Excessive levels of VEGF promote choroidal neovascularization and thereby contribute to the pathogenesis of wet age-related macular degeneration (AMD). Intravitreal anti-VEGF injections am...

To maintain homeostasis, cells have evolved stress-response pathways to cope with exogenous and endogenous stress factors. Diverse stresses at high doses may be detrimental, albeit low doses of stress, known as hormesis, can be beneficial. Upon exposure to stress, such as temperature rise, the conventional heat shock response (HSR) regulated by the...

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population with limited understanding of its pathogenesis and a lack of effective treatment. The progression of AMD is initially characterized by atrophic alterations in the retinal pigment epithelium, as well as the formation of lysosomal lipofuscin and e...

The published article [...]

Population isolates such as Finland provide benefits in genetic studies because the allelic spectrum of damaging alleles in any gene is often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%), which survived the founding bottleneck, as opposed to being distributed over a much larger number of ultra--rare...

Dry age-related macular degeneration (AMD) is a currently untreatable vision threatening disease. Impaired proteasomal clearance and autophagy in the retinal pigment epithelium (RPE) and subsequent photoreceptor damage are connected with dry AMD, but detailed pathophysiology is still unclear. In this paper, we discover inhibition of cytosolic prote...

Purpose Cigarette smoke increases the risk for age-related macular degeneration (AMD) e.g. through oxidative stress and mitochondrial damage in human retinal pigment epithelial (RPE) cells. Vascular endothelial growth factor (VEGF) promotes choroidal neovascularization in wet AMD, for which anti-VEGF injections are used as therapy. Since VEGF is im...

Purpose The exact mechanisms underlying the age-related macular degeneration (AMD) are still not totally understood, but processes like inflammation, chronic oxidative stress (OS), and autophagy impairment, are currently believed to have strong influence of the disease development. There are multiple studies concerning changes of the proteome in di...

Purpose To see if patients with wet age-related macular degeneration (wAMD) have significant changes in their systemic levels of epithelial-mesenchymal transition (EMT)-related serum markers. Methods We compared 71 Finnish wAMD patients undergoing anti-VEGF-A (vascular endothelial growth factor A) treatments to 64 age-adjusted controls. The serum...

Purpose Age-related macular degeneration (AMD) can be classified as an aggregation disease where cellular protein waste starts to accumulate in the retinal pigment epithelial (RPE) cells. Decline of autophagy and dysfunction of proteasomes have been identified as one the main reasons for the eventually detrimental protein aggregation. p38/mitogen-a...

Purpose Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g. age-related macular degeneration (AMD). Previously, we reported elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the pigment epithelial (RPE) cells of dry AMD-like nuclear...

Purpose Disturbed proteostasis and protein aggregation have a key role in Alzheimer´s disease and age-related macular degeneration pathology. In this study, we assessed the electrophysiological and protein aggregation related biomarker changes in 5xFAD mouse model. Methods Scotopic and photopic electroretinograms (ERG) were recorded at 3, 6, 9 and...

Purpose Chronic oxidative stress eventually leads to protein aggregation in combination with impaired autophagy, which has been observed in age-related macular degeneration (AMD). We have recently developed a dry AMD mice model with a nuclear factor-erythroid 2-related factor-2 (NFE2L2) knock-out (KO). Pinosylvin, a polyphenol abundant in bark wast...

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this met...

Chronic oxidative stress eventually leads to protein aggregation in combination with impaired autophagy, which has been observed in age-related macular degeneration. We have previously shown an effective age-related macular degeneration disease model in mice with nuclear factor-erythroid 2-related factor-2 (NFE2L2) knockout. We have also shown pino...

Background The insulin/IGF-1 signaling pathway has a major role in the regulation of longevity both in Caenorhabditis elegans and mammalian species, i.e., reduced activity of this pathway extends lifespan, whereas increased activity accelerates the aging process. The insulin/IGF-1 pathway controls protein and energy metabolism as well as the prolif...

Purpose It has been hypothesized that epithelial–mesenchymal transition (EMT) may occur in the retinal pigment epithelium of advanced stage age-related macular degeneration (AMD). Various serum and plasma growth factors and inflammatory mediators have been linked to AMD. We were interested in finding out whether systemic levels of EMT-associated ma...

The unique anatomy of the eye and the presence of various biological barriers make efficacious ocular drug delivery challenging, particularly in the treatment of posterior eye diseases. This review focuses on the combination of ultrasound and microbubbles (USMB) as a minimally invasive method to improve the efficacy and targeting of ocular drug del...

Introduction: Age-related macular degeneration (AMD) is the leading, cause of sight loss in the elderly in the Western world. Most patients remain still without any treatment options. The targeting of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a transcription co-factor, is a putative therapy against AMD. Areas...

Recent genetic and molecular studies have indicated that the innate immune system, especially microglia, have a crucial role in the accumulation of β-amyloid plaques in Alzheimer's disease (AD). In particular, the CD33 receptor, also called Siglec-3, inhibits the TREM2 receptor-induced phagocytic activity of microglia. CD33 receptors recognize the...

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population with poorly known pathogenesis and lack of effective treatment. Age and family history are the strongest AMD risk factors, and several loci were identified to contribute to AMD. Recently, also the epigenetic profile was associated with AMD, and...

Macular edema and its further complications due to the leakage from the choroidal neovascularization in course of the age-related macular degeneration (AMD) is a leading cause of blindness among elderly individuals in developed countries. Changes in tear film proteomic composition have been reported to occur in various ophthalmic and systemic disea...

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment ep...

Age-related macular degeneration (AMD), the main cause of vision loss in the elderly, is associated with oxidation in the retina cells promoting telomere attrition. Activation of telomerase was reported to improve macular functions in AMD patients. The catalytic subunit of human telomerase (hTERT) may directly interact with proteins important for s...

Age-related macular degeneration (AMD) is a severe retinal eye disease where dysfunctional mitochondria and damaged mitochondrial DNA in retinal pigment epithelium (RPE) have been demonstrated to underlie the pathogenesis of this devastating disease. In the present study, we aimed to examine whether damaged mitochondria induce inflammasome activati...

Inflammation is a key underlying factor of age-related macular degeneration (AMD) and inflammasome activation has been linked to disease development. Induced pluripotent stem-cell-derived retinal pigment epithelial cells (iPSC-RPE) are an attractive novel model system that can help to further elucidate disease pathways of this complex disease. Here...

Age-related macular degeneration (AMD) is a retinal disease leading to impaired vision. Cigarette smoke increases the risk for developing AMD by causing increased reactive oxygen species (ROS) production and damage in the retinal pigment epithelium (RPE). We have previously shown that the cigarette tar component hydroquinone causes oxidative stress...

Importance The c.1102C>T, p.(Gln368Ter) variant in the myocilin (MYOC) gene is a known risk allele for glaucoma. It is the most common MYOC risk variant for glaucoma among individuals of European ancestry, and its prevalence is highest in Finland. Furthermore, exfoliation syndrome has high prevalence in Scandinavia, making the Finnish population id...

Chronic inflammation has been associated with several chronic diseases, such as age-related macular degeneration (AMD). The NLRP3 inflammasome is a central proinflammatory signaling complex that triggers caspase-1 activation leading to the maturation of IL-1β. We have previously shown that the inhibition of the chaperone protein, Hsp90, prevents NL...

Background Wet age‐related macular degeneration (AMD) and age‐related cataract are often coexisting causes of visual impairment. Yet, the timing of cataract surgery in wet AMD patients is controversial. Methods One hundred and eleven eyes of 111 patients with wet AMD underwent cataract surgery at Helsinki University Hospital in Finland during 2014...

Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. In our previous studies, we found that deficiencies in the nuclear factor, erythroid 2 like 2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) genes caused AMD-like pathological pheno...

Age-related macular degeneration (AMD) is a progressive sight-impairing disease of the elderly. The pathogenic mechanisms of AMD are not well understood although both genetic and many environmental factors have been associated with the development of AMD. One clinical hallmark of AMD is the detrimental aggregation of damaged proteins. Recently, it...

Purpose Age‐related macular degeneration (AMD) is a multifactorial disease, and a leading cause of blindness elderly in the developed countries. In its neovascular form, an immediate treatment is required to maintain the best possible vision. The better understanding of the mechanisms underlying AMD is needed to create a both new treatment protocol...

Age-related macular degeneration (AMD) is an eye disease in which retinal pigment epithelium (RPE) cells play a crucial role in maintaining retinal homeostasis and photoreceptors’ functionality. During disease progression, there is increased inflammation with nucleotide-binding domain, leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome ac...

Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of...