The Rationale for Photobiomodulation Therapy of Vaginal Tissue for Treatment of Genitourinary Syndrome of Menopause: An Analysis of Its Mechanism of Action, and Current Clinical Outcomes.

Objective: Light, particularly in the visible to far-infrared spectrum, has been applied to the female genital tract with lasers and other devices for nearly 50 years. These have included procedures on both normal and neoplastic tissues, management of condylomata, endometriosis, and menometrorrhagia, and, more recently, a number of fractional laser devices have been applied for the management of genitourinary syndrome of menopause (GSM) and stress urinary incontinence (SUI), and to achieve so-called vaginal rejuvenation. Photobiomodulation therapy (PBMT) has been proposed as an alternative for use in managing GSM and SUI. Methods: This article reviews the biological basis, symptoms, and management of GSM, and investigates the current status and rationale for the use of PBMT. Results and conclusions: Based on the preliminary evidence available, PBMT is safe and appears to be efficacious in treating GSM.

Flexible quantum dot light-emitting devices for targeted photomedical applications.

Quantum dot light-emitting devices (QLEDs), originally developed for displays, were recently demonstrated to be promising light sources for various photomedical applications, including photodynamic therapy cancer cell treatment and photobimodulation cell metabolism enhancement. With exceptional emission wavelength tunability and potential flexibility, QLEDs could enable wearable, targeted photomedicine with maximized absorption of different medical photosensitizers. In this paper, we report, for the first time, the in vitro study to demonstrate that QLEDs-based photodynamic therapy can effectively kill Methicillin-resistant Staphylococcus aureus, an antibiotic-resistant bacterium. We then present successful synthesis of highly efficient quantum dots with narrow spectra and specific peak wavelengths to match the absorption peaks of different photosensitizers for targeted photomedicine. Flexible QLEDs with a peak external quantum efficiency of 8.2% and a luminance of over 20,000 cd/m2 at a low driving voltage of 6 V were achieved. The tunable, flexible QLEDs could be employed for oral cancer treatment or diabetic wound repairs in the near future. These results represent one fresh stride toward realizing QLEDs' long-term goal to enable the wide clinical adoption of photomedicine.

Optogenetic regulation of transcription.

Optogenetics has become widely recognized for its success in real-time control of brain neurons by utilizing non-mammalian photosensitive proteins to open or close membrane channels. Here we review a less well known type of optogenetic constructs that employs photosensitive proteins to transduce the signal to regulate gene transcription, and its possible use in medicine. One of the problems with existing gene therapies is that they could remain active indefinitely while not allowing regulated transgene production on demand. Optogenetic regulation of transcription (ORT) could potentially be used to regulate the production of a biological drug in situ, by repeatedly applying light to the tissue, and inducing expression of therapeutic transgenes when needed. Red and near infrared wavelengths, which are capable of penetration into tissues, have potential for therapeutic applications. Existing ORT systems are reviewed herein with these considerations in mind.

Quantum dot light emitting devices for photomedical applications.

While OLEDs have struggled to find a niche lighting application that can fully take advantage of their unique form factors as thin, flexible, lightweight and uniformly large-area luminaire, photomedical researchers have been in search of low-cost, effective illumination devices with such form factors that could facilitate widespread clinical applications of photodynamic therapy (PDT) or photobiomodulation (PBM). Although existing OLEDs with either fluorescent or phosphorescent emitters cannot achieve the required high power density at the right wavelength windows for photomedicine, the recently developed ultrabright and efficient deep red quantum dot light emitting devices (QLEDs) can nicely fit into this niche. Here, we report for the first time the in-vitro study to demonstrate that this QLED-based photomedical approach could increase cell metabolism over control systems for PBM and kill cancerous cells efficiently for PDT. The perspective of developing wavelength-specific, flexible QLEDs for two critical photomedical fields (wound repair and cancer treatment) will be presented with their potential impacts summarized. The work promises to generate flexible QLED-based light sources that could enable the widespread use and clinical acceptance of photomedical strategies including PDT and PBM.

Red Light Modulates Ultraviolet-Induced Gene Expression in the Epidermis of Hairless Mice.

OBJECTIVE: The purpose of this study was to investigate whether low-level light therapy (LLLT) was capable of modulating expression of ultraviolet (UV) light-responsive genes in vivo. MATERIALS AND METHODS: The effects of 670 nm light-emitting diode (LED) array irradiation were investigated in a hairless SHK-1 mouse epidermis model. Mice were given a single dose of UVA/UVB light, or three doses of red light (670 nm @ 8 mW/cm(2) x 312 sec, 2.5 J/cm(2) per session) spread over 24 h along with combinations of pre- and post-UV treatment with red light. Levels of 14 UV-responsive mRNAs were quantified 24 h after UV irradiation by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The transcription of mRNAs encoding for cluster of differentiation molecule 11b (CD11b) (p < 0.05) and interferon (IFN)-γ (p < 0.012) increased after irradiation with red light alone, whereas expression level of cyclooxygenase (COX)-2 (p < 0.02) was downregulated. Genes unresponsive to UV did not change their expression levels after exposure to red light either. Pretreatment with red light significantly modified response of Fos to UV exposure (p < 0.01). A synergy of UV and post-treatment with red light in reducing the transcription levels of CD11b (p < 0.05) and inducible nitric oxide synthase (iNOS) (p < 0.05) was observed. CONCLUSIONS: This is an initial observation that in mouse red light LLLT more often than not causes opposite gene expression changes or reduces those caused by moderate UVA-UVB irradiation.

The growth of human scalp hair in females using visible red light laser and LED sources.

BACKGROUND AND OBJECTIVES: Low level laser (light) therapy (LLLT) has been demonstrated to promote hair growth in males. A double-blind randomized controlled trial was undertaken to define the safety and physiologic effects of LLLT on females with androgenic alopecia. METHODS: Forty-seven females (18-60 years old, Fitzpatrick I-IV, and Ludwig-Savin Baldness Scale I-2, I-3, I-4, II-1, II-2 baldness patterns) were recruited. A transition zone scalp site was selected; hairs were trimmed to 3 mm height; the area was tattooed and photographed. The active group received a "TOPHAT655" unit containing 21, 5 mW diode lasers (655 ± 5 nm) and 30 LEDS (655 ± 20 nm), in a bicycle-helmet like apparatus. The placebo group unit appeared identical, containing incandescent red lights. Patients treated at home every other day × 16 weeks (60 treatments, 67 J/cm(2) irradiance/25 minute treatment, 2.9 J dose), with follow up and photography at 16 weeks. A masked 2.85 cm(2) photographic area was evaluated by another blinded investigator. The primary endpoint was the percent increase in hair counts from baseline. RESULTS: Forty-two patients completed the study (24 active, 18 sham). No adverse events or side effects were reported. Baseline hair counts were 228.2 ± 133.4 (N = 18) in the sham and 209.6 ± 118.5 (N = 24) in the active group (P = 0.642). Post Treatment hair counts were 252.1 ± 143.3 (N = 18) in the sham group and 309.9 ± 166.6 (N = 24) in the active group (P = 0.235). The change in hair counts over baseline was 23.9 ± 30.1 (N = 18) in the sham group and 100.3 ± 53.4 (N = 24) in the active group (P < 0.0001). The percent hair increase over the duration of the study was 11.05 ± 48.30 (N = 18) for the sham group and 48.07 ± 17.61 (N = 24) for the active group (P < 0.001). This demonstrates a 37% increase in hair growth in the active treatment group as compared to the placebo group. CONCLUSIONS: LLLT of the scalp at 655 nm significantly improved hair counts in women with androgenetic alopecia at a rate similar to that observed in males using the same parameters.

The growth of human scalp hair mediated by visible red light laser and LED sources in males.

BACKGROUND AND OBJECTIVES: Low level laser therapy (LLLT) has been used to promote hair growth. A double-blind randomized controlled trial was undertaken to define the safety and physiologic effects of LLLT on males with androgenic alopecia. METHODS: Forty-four males (18-48 yo, Fitzpatrick I-IV, Hamilton-Norwood IIa-V) were recruited. A transition zone scalp site was selected; hairs were trimmed to 3 mm height; the area was tattooed and photographed. The active group received a "TOPHAT655" unit containing 21, 5 mW lasers (655 ± 5 nm), and 30 LEDS (655 ± 20 nm), in a bicycle-helmet like apparatus. The placebo group unit appeared identical, containing incandescent red lights. Patients treated at home every other day × 16 weeks (60 treatments, 67.3 J/cm(2) irradiance/25 minute treatment), with follow up and photography at 16 weeks. A masked 2.85 cm(2) photographic area was evaluated by another blinded investigator. The primary endpoint was the percent increase in hair counts from baseline. RESULTS: Forty-one patients completed the study (22 active, 19 placebo). No adverse events or side effects were reported. Baseline hair counts were 162.7 ± 95.9 (N = 22) in placebo and 142.0 ± 73.0 (N = 22) and active groups respectively (P = 0.426). Post Treatment hair counts were 162.4 ± 62.5 (N = 19) and 228.7 ± 102.8 (N = 22), respectively (P = 0.0161). A 39% percent hair increase was demonstrated (28.4 ± 46.2 placebo, N = 19; 67.2 ± 33.4, active, N = 22) (P = 0.001) Deleting one placebo group subject with a very high baseline count and a very large decrease, resulted in baseline hair counts of 151.1 ± 81.0 (N = 21) and 142.0 ± 73.0 (N = 22), respectively (P = 0.680). Post treatment hair counts were 158.2 ± 61.5 (N = 18) and 228.7 ± 102.8 (N = 22) (P = 0.011), resulting in a 35% percent increase in hair growth (32.3 ± 44.2, placebo, N = 18; 67.2 ± 33.4, active, N = 22) (P = 0.003). CONCLUSIONS: LLLT of the scalp at 655 nm significantly improved hair counts in males with androgenetic alopecia.

Preliminary assessment of photoactivated antimicrobial collagen on bioburden in a murine pressure ulcer model.

OBJECTIVE AND BACKGROUND DATA: Overcoming bacterial antibiotic resistance requires alternative strategies. The ability of photoactivated collagen-embedded flavins (PCF) to reduce bioburden in infected pressure ulcers was investigated. DESIGN AND METHODS: Two pressure ulcers were created on the dorsum of female BALB/C mice (n=40, 35 g) maintaining a 5 mm skin bridge between lesions. Ulcers and surrounding skin were covered with Tegaderm™ and inoculated with 0.1 mL of 1 × 10(5) colony-forming units (CFU)/mL methicillin-resistant Staphylococcus aureus (MRSA). Fluid was permitted to reabsorb for 10 min. In experiment 1, one wound from each animal was treated using PCF and photoradiation (PCF+R, n=12) or photoradiation alone (R, n=11). Composite dressing-treated wounds received 1 × 1 cm PCF discs. Overlying Tegaderm was excised, and PCF was placed over the wound and again covered with Tegaderm. Wounds were irradiated at 455 ± 5 nm (350 mW, 1 cm spot diameter, 15 min) using a diode laser 10 min after placement. Controls received no PCF or photoradiation (C, n=12). Animals were euthanized 24 h post-therapy. Quantitative bacterial counts (CFU/g tissue) were determined. In experiment 2, composite dressing-treated wounds were irradiated at 455 ± 5 nm (350 mW, 1 cm spot diameter, 15 min) using a diode laser 10 min after daily PCF placement (0, 1, 2, or 3 treatments, n=8/group). Controls received no treatment. Wounds were cultured daily. Animals were euthanized on day 7 post-infection. Quantitative bacterial counts were determined. RESULTS: PCF+R significantly reduced bacterial counts at 24 h (experiment 1, p<0.0001; experiment 2, p<0.05). The bacterial counts in rats receiving photoradiation alone were no different from those of untreated controls (experiment 1, p=0.24). PCF+R produced a 2-3 log reduction in bacterial counts (experiment 2, p<0.001). Antibacterial effects increased with number of treatments, and persisted for several days post-therapy (p<0.002). CONCLUSIONS: PCF+R inhibited bacterial growth in this model. This effect increased with successive treatments, persisting several days post-therapy. Further studies to optimize this treatment modality are warranted.